Reduction Of Proteinuria Research Articles

#634 Prognosis is still poor in patients with posttransplant C3 glomerulopathy: a multicenter cohort

Abstract Background and Aims Data on patients with posttransplant recurrent or de novo C3 glomerulopathy (C3G) are limited. We therefore aimed to analyze features and outcomes of patients developed posttransplant C3G. Method In this retrospective multicenter study conducted across 3 centers, we collected the data of kidney transplant recipients (KTRs) who were diagnosed with posttransplant recurrent or de novo C3G between 2014-2023 and followed for at least 3 months after the diagnosis. Demographic, clinical, laboratory and histopathological characteristics of patients were retrieved from the databases of participating centers. Primary outcome was defined as death-censored graft loss necessitating dialysis or re-transplantation, and secondary outcome was complete (CR) or partial remission (PR). CR was the recovery of baseline eGFR and proteinuria of <0.5 g/g. PR was ≥50% reduction of proteinuria (and to <3 g/g in patients with nephrotic-range proteinuria at baseline) plus stabilization or improvement in kidney function. Results Eleven patients were identified, and 10 with follow-up data were included. Detailed features of patients were shown in the Table. Five (50%) were male, and mean age at the time of transplantation (KTx) was 33.2 ± 8.5 years. Nine KTRs (90%) were diagnosed with recurrent C3G and the etiology of primary kidney disease was not known in one patient. Majority of KTx were performed from living donors (9.90%). One patient had a history of T-cell mediated rejection before posttransplant C3G, which had showed good response to anti-rejection treatment. Posttransplant C3G was diagnosed after a median of 26 (3-85) months after KTx, and mean age was 36.8 ± 9.1 years. Mean hemoglobin, serum creatinine, serum albumin, and proteinuria at the time of diagnosis were 10.5 ± 1.8 g/dl, 1.9 ± 0.7 mg/dl, 4.1 ± 0.5 g/dl, and 1.1 ± 0.9 g/g, respectively. Monoclonal disorders were excluded by using serum and urine electrophoresis and serum free light chain assays in all KTRs. Serum C3 was low (67.1 ± 29.7 mg/dl, ref: 90-180 mg/dl) in 7 of 8 KTRs with available data (87.5%). Further immunosuppressive treatment was administered in 9 cases. Eculizumab was used in 8, and 1 patient was treated with pulse steroids and therapeutic plasma exchange. Median duration of treatment was 14.5 (3-24.3) months. Four patients (44.4%) who were treated with eculizumab showed CR. After a median of 32 (9.5-82) months, 5 KTRs (50%) experienced graft loss despite eculizumab use in 3 of them. No adverse events attributed to treatment were observed. Conclusion Prognosis is still quite dismal in patients with posttransplant C3G despite the use of eculizumab. Better treatment options are urgently needed.

#2631 Efficacy and safety of Telitacicept combined with low-dose mycophenolate mofetil in IgA nephropathy

Abstract Background and Aims Currently, there is no specific agent blocking for IgA nephropathy. The KDIGO guideline recommends basic treatment with renin-angiotensin-aldosterone system (RAAS) antagonists. MMF can be used for Chinese patients. Telitacicept is a fusion protein composed of transmembrane activator and calcium modulating cyclophilin ligand interactor and fragment crystallizable portion of immunoglobulin G (IgG), which neutralizes the B lymphocyte stimulator and a proliferation-inducing ligand. Telitacicept (240 mg qw ih) treatment led to a clinically meaningful reduction in proteinuria in patients with IgAN in the present phase 2 clinical trial. This study intends to observe the efficacy of Telitacicept (160 mg qw ih) combined with low-dose MMF in the treatment of IgA nephropathy. Method Retrospective analysis involving all biopsy proven IgA nephropathy patients with complete clinical data in our department. After RAAS inhibitor treatment for 3 months, the patient's urinary protein more than 0.75 g/24 h, he or she was given Telitacicept (160 mg qw) combined with Mycophenolate mofetil (1 g, twice a day) was treated for 6 months, and follow-up for 6-12 months. The quantification of 24-hour urinary protein and immunity functional, renal function was observed. Results 25 patients with IgA nephropathy confirmed by renal biopsy were enrolled, 14 males and 11 females, aged 34.32 ± 9.68 years’ old, 3 patients with Lee's grade II, Grade III 17 patients, Grade IV 3 patients, and Grade V 2 patients. For Oxford classification, there were 3 cases with M0, 22 cases with M1 lesions, 20 cases with E0, 5 cases with E1 lesions, 1 case with S0, 24 cases with S1 lesions, 10 cases with T0, 15 cases with T1 lesions, and 17 cases with C0, 8 cases with C1 lesions. The patient's urine protein quantification was 2.52 ± 1.82 g before treatment, after Telitacicept and MMF treatment for 2 months, the proteinuria was 1.05 ± 0.55 g (compared with that before treatment, P = 0.0004), and at 4 months, it was 0.71 ± 0.39 g (compared with that before treatment, P < 0.0001), 0.53 ± 0.31 g at 6 months (compared with than before treatment, P < 0.0001). And the 24-hour urine protein quantification of 13 patients was all lower than 0.5 g/24 hours. The renal function of all patients was stable during the observation period. The serum creatinine before treatment was 83.16 ± 21.85 μmol/L and it was 81.88 ± 19.48 μmol/L (P = 0.83) after 6 months. There were no patients with worsening renal function after treatment. Among them, the renal function of 3 patients was better than that after treatment. During follow-up period for 6- to 12-month, the patient did not develop any pulmonary infection requiring for hospitalization or other infections. Some patients experienced adverse reactions such as pain at the site of injection, but no patient discontinued treatment due to adverse reactions. Conclusion Telitacicept combined with low-dose mycophenolate mofetil is a alternative method for the treatment of IgA nephropathy. It is more effective than mycophenolate mofetil or Telitacicept use alone, and with fewer adverse reactions, especially with S or C lesions of Oxford classification. This is an observational retrospective study with a few cases, it's worthy further randomized clinical study to prove.

#456 Efficacy and safety of iptacopan in patients with primary IgA nephropathy: interim analysis results of the Phase 3 APPLAUSE-IgAN study

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. An unmet need for targeted disease-modifying treatments addressing its pathophysiology remains. There is compelling evidence for involvement of the alternative complement pathway (AP) in IgAN. Iptacopan binds to Factor B and specifically inhibits the AP. The APPLAUSE-IgAN trial is evaluating the efficacy and safety of iptacopan vs placebo, on top of optimized supportive therapy, in patients with IgAN. Here we present the results of the pre-specified interim analysis (IA) with a focus on the results for key subgroups. Method APPLAUSE-IgAN (NCT04578834), a Phase 3, multicentre, randomised, double-blind, placebo-controlled trial, enrolled adults with biopsy-confirmed IgAN with proteinuria ≥1 g/g by urine−protein creatinine ratio from 24-hour urine collection (UPCR-24h) despite being on a stable dose of maximally tolerated renin-angiotensin-system inhibition (RASi) for 3 months, with or without other background therapy such as sodium-glucose transport protein 2 inhibition (SGLT2i). Patients were randomized 1:1 to iptacopan 200 mg or placebo twice daily for 24 months while remaining on stable supportive therapy. The primary objective of the prespecified IA was to demonstrate superiority of iptacopan vs placebo in reducing UPCR-24h at Month 9 (M9) in the main study population (estimated glomerular filtration rate [eGFR] ≥30 mL/min/1.73 m2 at baseline). Subgroup analyses included baseline age, sex, Asia vs non-Asia region, proteinuria, eGFR, and SGLT2i use. Efficacy analyses were performed on the first 250 patients (n = 125 each for iptacopan and placebo) who reached the M9 visit or discontinued from the study. Safety analyses included all patients of the main population who had received treatment by the time of the IA (iptacopan, n = 222; placebo, n = 221). Results Baseline demographics and disease characteristics were similar between the two arms (Table) and indicative of patients at high risk of IgAN disease progression. Iptacopan was superior to placebo in reducing proteinuria, with reduction in UPCR-24h at M9 relative to baseline of 38.3% (95% CI: 26.0%, 48.6%; 1-sided p < 0.0001) vs placebo (Figure). Subgroup analyses showed that treatment effect consistently favoured iptacopan regardless of baseline age, sex, Asia vs non-Asia region, UPCR-24h or eGFR levels, or SGLT2i use as part of the supportive care (Figure). Treatment-emergent adverse events (TEAEs) occurred in 138 (62.2%) iptacopan vs 153 (69.2%) placebo patients, with the majority being of mild to moderate severity. Treatment-emergent serious AEs were reported in 18 (8.1%) and 11 (5.0%) patients in the iptacopan and placebo arms, respectively. TEAEs leading to treatment discontinuation occurred in 6 patients (2.7%) in each arm. No deaths were reported. Iptacopan treatment did not lead to clinically relevant differences in total cholesterol, low-density lipoprotein cholesterol, and serum triglycerides compared with placebo. Conclusion APPLAUSE-IgAN, the first Phase 3 study confirming the relevance of the AP in IgAN, demonstrated superiority of iptacopan vs placebo, with a significant reduction in proteinuria at M9 (38.3%) that was consistent across key subgroups evaluated. Iptacopan was well tolerated with a favourable safety profile.

#1609 Effect of dapagliflozin in proteinuria reduction and glomerular filtration rate in a group of Alport syndrome patients

Abstract Background and Aims Alport syndrome (AS) is the most common cause of inherited chronic kidney disease. This disorder is caused by deleterious variants on COL4A3, COL4A4 or COL4A5 genes. These genes codify the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing the leakage of red blood cells and proteins, mainly albumin, into the urine resulting in kidney damage and loss of renal function. In AS progressive kidney impairment can be delayed or possibly prevented by timely initiation of renin angiotensin aldosterone inhibitors (RAAi): in males with X-linked AS and in autosomal recessive AS ARAS at diagnosis and in females with XLAS and autosomal dominant AS at the onset of microalbuminuria. Recently, it was showed that sodium-cotransporter-2 inhibitors (SGLT2i) reduce proteinuria and slow the progression of kidney disease in many glomerular diseases. Thus, also in AS, SGLT2i could be promising in renal disease progression control. The aim of this study was to determine the proteinuria reduction and the effect on the glomerular filtration rate (GFR) in a group of AS patients with persistent proteinuria besides the use of RAAi in maximum tolerated doses after adding SGLT2i to the treatment. Method This study was single-center, observational and prospective study evolving 8 AS adult patients, without a diagnosis of diabetes, with persistent proteinuria besides the use of RAAi in maximum tolerated doses. All patients were prescribed wit dapagliflozin 10 mg daily. We determine the changes from baseline of urinary protein/creatine (Up/cr) and glomerular filtration rate (based on epiGFR formula). Results Eight AS patients were included in this study. All were male patients. One patient has XLAS and the other 7 patients have ADAS. No patient was diabetic, and all were under RAAi in maximum tolerated doses. We determine de Up/cr and epiGFR at baseline and median time of 213.5 days (IQR 208.3-259) after SGLT2i initiation. At baseline, the median of Up/cr was 1.4 (IQR 0.8-2.1) and after SGLT2i Up/cr was 1.5 (0.8-2.6), p = 0.727. Up/cr, after SGLT2i treatment, reduced in 3 patients and worsened in 5. Median epiGFR at baseline was 80.3 ml/min (IQR 40.9-109.5) and after SGLT2i initiation was 74.7 ml/min (40.4-112.0), p = 0.727. Conclusion In this study, we did not observe an improvement in Up/cr of AS patients with SGLT2i treatment. A slight decrease in GFR was observed that may be due to the well know hemodynamic effects of SGLT2i. The small cohort and short time of the study are factors that can interfere in these results and should not discourage the treatment of AS patients with SGLT2i.

#3108 Rituximab in adult-onset IgA vasculitis

Abstract Background and Aims Adult-onset IgA Vasculitis (IgAV) is poorly responsive to glucocorticoids (GC) and conventional immunosuppressive therapies, such as cyclophosphamide. Rituximab has been successfully used in a few cases and may represent a safer and potentially more effective option [1]. Crescentic IgA Nephropathy (cIgAN), a rare entity that shares features of renal vasculitis with IgAV, is also frequently refractory to cyclophosphamide, while response to rituximab is unknown. We investigated outcomes after rituximab in a multicentre European cohort of adult-onset IgAV and cIgAN. Method We screened clinical records of patients followed at 18 European consorted centres who were ≥18 years old at the onset of IgAV and received ≥1 rituximab dose. Furthermore, we identified patients with cIgAN (≥25% crescentic glomeruli and rapidly progressive glomerulonephritis), who were treated with rituximab. Remission was defined as Birmingham Vasculitis Activity Score (BVAS) <3 at month 6 after rituximab and renal response as stable or improved eGFR and ≥50% proteinuria reduction. Relapse was defined as an increase in BVAS requiring a change in immunosuppressive therapy. Outcomes of IgAV with severe nephritis (eGFR <60 mL/min) were compared with those of cIgAN. Results We included 61 patients with IgAV and 15 with cIgAN (Table). Rituximab was administered as initial therapy in 23/61 (38%) patients with IgAV and 13/15 with cIgAN (87%), while the remainder had refractory or relapsing disease. Active skin involvement was present in 49 patients (80%) and nephritis in 55 patients (90%) with IgAV at the time of starting rituximab. This was given alone in 13/61 (21%) or combined with GC in 48 (79%) patients with IgAV and in all those with cIgAN. Furthermore, cyclophosphamide was used in 15% of patients with IgAV and 40% of those with cIgAN. Remission at 6 months was achieved by 52 (85%) patients with IgAV and 12/13 (92%) of those treated with rituximab alone. A renal response was observed among 49/55 (89%) of those with nephritis. Patients with IgAV and severe nephritis had similar eGFR to those with cIgAN at the time of starting rituximab, but the latter had lower rate of remission and a higher frequency of kidney failure. A relapse occurred in 15/52 patients (29%) who achieved remission a median of 13 months (10-15) after rituximab. Eight patients resumed rituximab and achieved again remission. Conclusion Rituximab alone or in combination with GC and immunosuppressants appeared to achieve a high rate of remission in this cohort of adult-onset IgAV. Renal response among those with severe nephritis was also good, while this was worse among patients with cIgAN, suggesting substantial differences among these conditions despite similar histological appearances.

#2572 Sodium-glucose transport protein 2 (SGLT-2) inhibitors in diabetic and non-diabetic kidney transplant recipients

Abstract Background and Aims The beneficial effects of administering sodium-glucose transport protein 2 (SGLT2i) inhibitors in patients with Chronic Kidney Disease, with or without Type 2 Diabetes (T2D), has been proven in large randomized controlled trials. Nevertheless, there is limited data considering Kidney Transplant Recipients (KTRs) with or without albuminuria. The purpose of this study was to evaluate the safety and efficacy of administering SGLT2i to KTRs in association to their kidney function and albuminuria. Method In this retrospective study we examined the effects of treatment with SGLT2i on kidney function (eGFR calculated with CKD-EPI formula), albuminuria (24h urine collection) and fasting serum glucose levels of KTRs. We included KTRs with T2D or without T2D and confirmed albuminuria (ACR >30 mg/gCr) in two consecutive ACR measurements. Kidney function and albuminuria monitoring was performed one month post-treatment initiation and in three month intervals thereafter. Moreover, immunosuppression trough levels were measured in each visit and active surveillance for adverse events was performed. Results Twenty-four KTRs (20 males) with a mean eGFR of 51.1 ± 14.2 ml/min/1.73 m2 were included in this study. Nine patients had T2D. Treatment was initiated 10 ± 5.4 years post transplant and all KTRs received dapagliflozin. Mean follow-up was 9 ± 2 months. Kidney function was non-significantly decreased directly after SGLT2i initiation and remained stable until the end of follow up (51.1 ± 14.2 vs. 51.4 ± 13.8 ml/min/1.73 m2). Overall, we found a significant reduction of albuminuria (371 ± 460 vs 235 ± 294 mg/24 h, p = 0.015). When KTRs were examined separately based on their diabetes status (KTRs with T2D vs. no T2D) we found that only those with T2D showed a significant decrease in albuminuria (450.4 ± 548 vs. 259.8 ± 332.5 mg/24 h, p = 0.008) at the end of follow up. Furthermore, a significant reduction of morning fasting glucose (106.4 ± 19.6 vs 99.9 ± 16.6 mg/dl, p = 0.0006) was noted. Trough levels of immunosuppression agents (tacrolimus, everolimus or cyclosporine) did not show any significant change after the initiation of SGLT2i and two patients had to discontinue the treatment, due to one episode of pyelonephritis and detection of funguria. Conclusion Prescription of SGTL2i in KTRs with T2D and albuminuria, seems to be a reliable option with significant efficacy on the decrease of albuminuria with minimal adverse effects.

#657 Obinutuzumab is effective for the treatment of frequently-relapsing/steroid-dependent minimal change disease in adults

Abstract Background and Aims Higher relapse rates and steroid dependency are challenges in the treatment of minimal change disease (MCD). The aim of this study was to evaluate the efficacy and safety of obinutuzumab, a humanised type II anti-CD20 monoclonal antibody, in adults with frequently relapsing (FR) or steroid-dependent (SD) minimal change disease (MCD). Method Patients with FR/SD MCD receiving obinutuzumab at our center between September 2022 and February 2023 were enrolled. Complete remission was defined as the reduction of proteinuria to 0.3g/d. The time to remission, the relapse rate, and adverse events were evaluated. Results Six patients with FR/SD MCD were included in the present study. The median age of the patients was 30.44 years (range 18.80-72.09 years) and 3 of them were male. Prior to treatment with obinutuzumab, five patients remained in nephrotic syndrome and one patient was in partial remission after previous treatment. One or two doses of 1g obinutuzumab were given. All six patients achieved a complete remission. Five patients with nephrotic syndrome achieved complete recovery within a range of 14 to 57 days. The patient, who initially achieved partial remission, reached complete remission within 27 days after receiving the first obinutuzumab dose. The average follow-up duration was 12.53 ± 1.97 months, during which there was no observed relapse. Furthermore, None of the patients experienced infusion-related adverse effects, serious infectious complications or neutropenia following treatment with obinutuzumab. Conclusion Obinutuzumab is an effective and safe treatment option for adult patients with FR/SD minimal change disease. Further randomized trials are needed to confirm these findings.

#2862 Genetics and electron microscopy: complementary tools for management of focal segmental glomerulosclerosis?

Abstract Background and Aims Focal segmental glomerular sclerosis (FSGS) defines a histologic lesion that represents a pattern of injury associated to different pathologic conditions affecting both children and adults. It is classified into primary forms, presumably immune-mediated, secondary forms, determined by a maladaptive response to different conditions, genetic and undetermined forms. According to Mayo Clinic classification, primary and secondary forms can de differentiated using electron microscopy (EM), with a podocytes foot process effacement (FPE) ≥80% identifying primary forms. Better understanding the role of Genetics in FSGS and response to treatment in different forms is of vital importance in this rare and multifaceted condition. We analyzed a discrete cohort of patients with FSGS examined both with EM and genetic testing (GT). Main aims of our study were: 1) assessment of GT in primary and secondary forms; 2) analysis of response to therapy according to histologic and genetic classification. Method This is a retrospective observational study on patients that received a histological diagnosis of FSGS, including EM, and underwent NGS genetic testing from January 2020 to June 2023. Primary and secondary forms of FSGS were distinguished by degree of pedicle fusion at EM, according to Mayo Clinic classification. Clinical, laboratory, genetic data and used therapies were recorded. Complete response (CR) to therapy was defined as a reduction of proteinuria to 0.3 g/day, with normalization of albuminemia. Partial response (PR) was defined as halving proteinuria into a sub-nephrotic range and increasing albuminemia up to 3.5 g/dL. Absent response was defined as a persisting nephrotic range proteinuria. Results In the study period, 33 patients receiving a histologic diagnosis of FSGS with EM examination underwent NGS testing. Of these, 25 had available genetic results and were included. Ten patients (40%) were females, 15 (60%) were males; mean age was 40.8 years (SD ±14.5); 20 (80%) were Caucasian, 4 (16%) Black, 1 (4%) Asian. Based on EM, 11 (44%) were classified as primary forms, 14 (56%) as secondary forms. Twelve (48%) patients presented with nephrotic syndrome. Of these, 10 had a primary form. Seven (28%) had nephrotic-range proteinuria without hypoalbuminemia, 6 (24%) had subnephrotic range proteinuria. Six (54.5%) of the primary forms and 8 (57.1%) of the secondary forms had a positive genetic testing (p = 0.78). Among secondary forms, through GT, one diagnosis of Fabry disease and one of Tuberous Sclerosis were made in patients without clear systemic symptoms. Fabry disease was confirmed by presence of zebra bodies at EM. All primary forms received immunosuppressive therapies, all being rituximab-based regimens; all secondary forms received support therapy. Nine (81.1%) primary forms and 9 (64.3%) secondary forms had at least a PR to treatment (4 CR in primary group and 1 CR in secondary group) (p = 0.33). Among primary forms, 5 of 6 patients (83%) with a positive GT had at least a PR with a strong immunosuppressive therapy. In secondary forms group 4 of 8 patients (50%) had at least PR with offered support therapy. Fabry and Tuberous Sclerosis were offered specific treatments with benefit. Conclusion Percentage of positive GT did not differ in primary and secondary forms of FSGS as defined by Mayo Clinic classification. Thus a positive GT should not be considered a unique feature of secondary forms. GT was critical for an unexpected diagnosis of systemic hereditary diseases, thus enabling adequate target therapies. We believe GT should be offered to all patients with FSGS. In primary FSGS, defined according to EM, more than 80% of patients had at least a PR following immunosuppressive therapy, even in patients with positive GT. In conclusion, as clinical presentation and light microscopy are not sufficient for an accurate diagnosis, combining EM and GT is of utmost importance in proper classification and management of FSGS.

#457 Sparsentan has direct effects on the glomerular capillary wall to attenuate increased permeability after exposure to nephrotic syndrome plasma

Abstract Background and Aims The glomerular endothelial glycocalyx (eGlx), a luminal layer of proteoglycans, glycoproteins and glycolipids, forms the first part of the glomerular filtration barrier (GFB). Nephrotic syndrome (NS) describes a group of pathologies of the renal glomerulus that result in proteinuria and is associated with glomerular endothelial dysfunction. Current treatments are broad and non-specific. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist that has received accelerated approval in the United States for the reduction of proteinuria in adults with IgA nephropathy at high risk of disease progression. Our validated glomerular permeability assay directly measures the albumin permeability (Ps’alb)of capillary loops within individually trapped glomeruli [1]. This ex vivo assay is independent of haemodynamic factors and tubular albumin handling – factors known to affect urine protein concentrations. This work examines whether sparsentan could reduce glomerular albumin permeability in NS, by preserving the eGlx to maintain the GFB. Method Human NS plasma samples were collected under ethical consent from 3 patients that had undergone plasma exchange from periods when they were in relapse (RL), or subsequent remission (RM). Adult male Sprague Dawley rats (175–200 g) were perfused with 4% Ringer BSA solution. Glomeruli were isolated on ice by graded sieving from the cortex of each kidney. Glomeruli were incubated, in the presence of AF488-conjugated BSA (AF488-BSA, 30 μg/ml) and R18 (36.5 μg/ml), with 10% plasma from NS patients for 1 hour, and simultaneously treated with sparsentan (0.1 μM, 1 μM and 10 μM) or vehicle. The glomerular Ps’alb assay was used to measure changes in albumin permeability. We applied a fluorescence profile peak-to-peak confocal imaging technique to treated glomeruli to assess glomerular eGlx thickness [2]. Results Human NS patients in RL had a significantly greater proteinuria compared to RM (RL, 10, 000 ± 1, 354 mg/g; RM, 95.3 ± 59.7 mg/g, P = 0.017). Incubation of rat glomeruli with RL plasma induced a significant increase in Ps’alb (RM+vehicle, 6.0 × 10−7 ± 0.12 × 10−7 cm/s; RL+vehicle, 10.9 × 10−7 ± 0.84 × 10−7 cm/s, P < .001) with a significant reduction in glomerular eGlx thickness (RM+vehicle, 210 ± 21.2 nm; RL+vehicle, 109 ± 7.9 nm, P = .027), compared to rat glomeruli incubated with paired RM plasma. Sparsentan-treated RL incubated glomeruli were protected from both the increase in Ps’alb (RL+spars 10 µM, 6.3 × 10−7 ± 0.19 × 10−7 cm/s, P < .001) and the loss in glomerular eGlx (RL+spars 10 µM, 222 ± 8.5 nm, P = .013), to a level comparable to RM incubated glomeruli. The effect of sparsentan on Ps’alb was dose dependent (RL+spars 1 µM, 8.0 × 10−7 ± 0.46 × 10−7 cm/s; RL+spars 0.1 µM, 9.6 × 10−7 ± 0.22 × 10−7 cm/s) with Ps’alb changes correlating inversely with glomerular eGlx thickness (r² = 0.75, P < .0001). In RM glomeruli, sparsentan alone had no effect on Ps’alb compared with vehicle (RM+spars 10 µM, 6.2 × 10−7 ± 0.25 × 10−7 cm/s, P = .590), suggesting no effect on otherwise healthy capillaries. Conclusion We have shown that dual inhibition of endothelin and angiotensin receptors, with sparsentan, preserves the glomerular eGlx resulting in normalised glomerular permeability in NS. These findings suggest that the direct action of sparsentan on the GFB could help maintain barrier integrity in NS, in particular by glycocalyx protection.

#3115 Effectiveness of SGLT2 inhibitors in patients with glomerulonephritis: a single center experience

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become widely used in recent years because of favorable outcomes on kidney function in people with diabetes mellitus and chronic kidney disease (CKD). The main effect of SGLT2 inhibitors is inhibiting sodium and glucose reabsorption, acting precisely in the early proximal tubule of the renal nephron. Although these drugs developed as glucose-lowering agents for their capability to induce glycosuria, cardiovascular outcome studies found that the reduction in kidney function was significantly delayed, and the incidence of severe decline in kidney function was reduced in patients taking SGLT2 inhibitors. Later on, these outcomes were confirmed by the results of the DAPA-CKD, EMPA-KIDNEY, and CREDENCE studies, which were specific outcome trials in patients with CKD. However, data about the use of SGLT2 inhibitors in patients with glomerulonephritis at routine clinical practice are still limited. The purpose of this study is to investigate the impact of SGLT2 inhibitors use in patients with glomerulonephritis. Method Patients diagnosed with biopsy-proven GN who continued their routine follow-up in Etlik City Hospital nephrology clinic were retrospectively examined. Patients with a steroid treatment history for GN were excluded from this study. We identified 29 patients who were treated with SGLT2 inhibitors for proteinuria. We analyzed the baseline characteristics, comorbidities, GN types, and laboratory parameters (baseline, sixth and twelfth months at the follow-up). Each patient was matched to the control with a similar baseline feature under conservative therapy (n = 29). Both patient groups were treated in line with the KDIGO glomerulonephritis guideline and were received RAAS blockers at the maximum tolerated dose. According to baseline levels, the reduction rate in proteinuria and eGFR of the sixth and twelfth months were calculated as percentages. The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design. Results Our study involved 58 patients diagnosed with 32 (55%) IgA nephropathy, 16 (28%) with membranous nephropathy, and 10 (17%) with focal segmental glomerulosclerosis. In the treatment group, 23 (79%) patients used dapagliflozin, and 6 (21%) used empagliflozin as SGLT2 inhibitors. Baseline proteinuria levels at [1940 (1780-2700 mg/d) vs. 1890 (1670-2400 mg/d); p = 0.8], eGFRs [60 (44-82) vs. 64 (46-80) ml/min/1.73 m2; p = 0.8] and serum albumin levels (39.6 ± 0.3 vs. 39.1 ± 0.2; p = 0.4) were similar between both groups. The proteinuria reduction rate in the sixth month was 34% (27.3-40.5) for the treatment group and 12% (6.9-20.7) for the control group (<0.0001). Besides, the reduction rate was still higher in the treatment group at the 12th month [50.5% (39-52.6) vs. 26.3% (17.2-35.4); p ≤ 0.0001]. eGFR declining rate at 6th months and 12th months were lower in SGLT2 group than the control group [3.1% (0-6.2) vs. 8.6% (4.1-16.6); p = 0.004 and 0.8% (0-5) vs. 5.9% (3.3-15.2); 0.005, respectively] (Table 1). Proteinuria levels at 6th months were 1170 (970-1890) mg/d and 1730 (1180-2100) mg/d for treatment and control group, respectively. At 12th months, median proteinuria level of SGLT2 group was 940 (840-1480) mg/d and control group was 1250 (1120- 2040) mg/d (Fig. 1). Conclusion In this study with a well-matched control group, we found that SGLT2 inhibitors demonstrate efficacy in mitigating the decline in estimated GFR and reducing albuminuria in patients with GN. However, randomized-controlled trials are still required specific to patients with GN.

#1549 The effect of sglt2 inhibitors (dapaglifozin) on albuminuria in patients of diabetic nephropathy above standard of care

Abstract Background and Aims Albuminuria is the hallmark of diabetic nephropathy (DN) and progression of albuminuria denotes declining renal functions culminating in End Stage Renal Disease. Intensive blood glucose control (HbA1c <7%), intensive blood pressure control (<130/90 mmHg), blockade of Renin Angiotensin Aldosterone System (RAAS) by Angiotensin converting enzyme inhibitors (ACE-i) and Angiotensin receptor blockers (ARBs) constitute the standard line of care for treatment of DN with proteinuria. Sodium Glucose cotransporter 2 inhibitors (SGLT2i) are drugs are recently introduced for proteinuria reduction with no data available in this part of the world. Hence, I, observed the antiproteinuric effect of SGLT2i in patients who have type2 diabetes mellitus (T2DM) with albuminuria and who are already on maximum doses of ACE-I or ARBs. My study population was on dapaglifozin due to easy availability and low cost. Method it is an observational study including patients who attended the out-patient clinic of Nephrology, at Medica Hospital, Kolkata between July 2022 to February 2023. Inclusion criteria: Exclusion criteria: Quantitative estimation of urine albumin was performed using the VITROS Chemistry Products mALB Reagent along with the VITROS Chemistry Products Calibrator Kit 24 on the VITROS 5,1 FS Chemistry System and the VITROS 5600 Integrated System. Blood sugar was measured by glucose oxidase method. eGFR by CKD EPI equation. Statistical Methodology Continuous variables were presented with mean and standard deviation and tested for normal distribution by the Kolmogorov-Smirnov test. Categorical variables were summarized using frequency and percentages. For testing of related samples, Wilcoxon sign ranked test is used. Statistical analyses were performed using the SPSS software with version 26.0. Results A total of 100 patients were included in the study, of which 3 patients were lost to follow up and 2 patients discontinued the study at 3 months due to fall in eGFR below 25 ml/min/1.73 m2 and 4 patients discontinued after 3 months because of fungal genital infections. After Dapaglifozin administration, a significant reduction in Urine Albumin-creatinine ratio (UACR) was observed, by a percentage decrease of 37.3% (p<0.001) at 3 months and of 70.2% (p<0.001) at 6 months from baseline. Similarly, there was an acute reduction in eGFR from baseline. A percentage decrease by 5.16% (p<0.001) was observed at 3 months & a decrease by 5.69% (p<0.001) at 6 months from baseline. Conclusion Conventional approaches reduce but have not been able to stop disease progression in Diabetic Kidney Disease (DKD). SGLT2i can protect against the onset of DKD, slow disease progression independently. They have an antiproteinuric effect in patients with diabetic nephropathy which was sustained throughout the follow-up period in my study. Studies have also shown that SGLT2i reduce major adverse cardiovascular events in patients with T2DM and established cardiovascular disease. With the new results of EMPA-KIDNEY trial, SGLT2i are being used at even lower eGFR (<25 ml/min/1.73 m2 till on hemodialysis) and such vast health benefits, invention of SGLT2i are is a boon to the mankind.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report

BackgroundLipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1–27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness.Case presentationA 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels.ConclusionHerein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Low-Protein Diet in Elderly Patients with Chronic Kidney Disease Stage 4 and 5 in Conservative Management: Focus on Sarcopenia Development.

Chronic kidney disease is a degenerative and increasingly prevalent condition that includes metabolic abnormalities and is associated with a higher risk of sarcopenia. The conservative approach points primarily to controlling metabolic issues and reducing the risk of malnutrition and sarcopenia, slowing the progression of kidney disease. The present study aims to evaluate the effect of a low-protein diet on malnutrition and sarcopenia. A total of 45 patients (33 male and 12 female) aged over 70 with chronic kidney disease stage 4-5 in conservative management were considered. All patients had a dietary assessment and prescription of personalized low-protein dietary plans (≤0.6 g protein/kg) and a follow-up control between 4 and 6 months. In preliminary and follow-up evaluations, anthropometric data, blood examinations, body composition results, muscle strength, physical performance, and a 3-day food diary were collected. In the follow-up period, a significant weight loss (p = 0.001) and a decrease in body mass index (p = 0.002) were recorded. Food diaries revealed a significant reduction in protein, sodium, potassium, and phosphorus intake (p < 0.001), with a significant reduction in urea (p < 0.001) and proteinuria (p = 0.01) without any impact on lean mass (p = 0.66). Considerable variations in adherence between food diaries and the prescribed diet were also noted. Providing a personalized low-protein diet led to significant benefits in a short period without worsening the patient's nutritional status.

Enteric-Coated Capsules Providing Reliable Site-Specific Drug Delivery to the Distal Ileum.

Nefecon, a targeted-release capsule formulation of budesonide approved for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy, targets overproduction of galactose-deficient immunoglobulin A type 1 in the Peyer's patches at the gut mucosal level. To investigate whether the commercial formulation of Nefecon capsules reliably releases budesonide to the distal ileum, a human study was conducted with test capsules reproducing the delayed-release function of Nefecon capsules. Caffeine was included in the test capsules as a marker for capsule opening in the gut since it appears rapidly in saliva after release from orally administered dosage forms. Magnetic resonance imaging with black iron oxide was used to determine the capsule's position in the gut at the time caffeine was first measured in saliva and additionally to directly visualize dispersion of the capsule contents in the gut. In vitro dissolution results confirmed that the test capsules had the same delayed-release characteristics as Nefecon capsules. In 10 of 12 human volunteers, the capsule was demonstrated to open in the distal ileum; in the other two subjects, it opened just past the ileocecal junction. These results compared favorably with the high degree of variability seen in other published imaging studies of delayed-release formulations targeting the gut. The test capsules were shown to reliably deliver their contents to the distal ileum, the region with the highest concentration of Peyer's patches.

Evaluating the cost-effectiveness of voclosporin for the treatment of lupus nephritis in the United States.

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; up to 30% of patients with LN will develop end-stage kidney disease (ESKD). One of the main treatment goals for LN is preservation of kidney function, with early decreases in proteinuria associated with improved long-term outcomes. Voclosporin, a second-generation calcineurin inhibitor, was approved in the United States in 2021 for the treatment of active LN combined with background immunosuppression. The AURORA 1 study found that the use of voclosporin with low doses of mycophenolate mofetil and glucocorticoids yielded significant reductions in proteinuria. The AURORA 2 study showed long-term efficacy and safety of voclosporin over a 3-year period with kidney function preservation. The Institute for Clinical and Economic Review (ICER) is a nonprofit organization that evaluates medical evidence to help improve patient outcomes and control costs. In 2021, ICER published an economic model to estimate the impact and cost-effectiveness of LN therapies. From a US health care perspective, voclosporin was cost-effective at $149,260 per quality-adjusted life-year (QALY) and $131,528 per equal value of life-years gained (evLYG). At the time of the LN cost-effectiveness model (CEM) development, voclosporin was not yet approved in the United States and the cost of treating patients with LN with ESKD was not captured in the literature. To evaluate the cost-effectiveness of voclosporin given the emergence of new data. The LN CEM uses a short-term trial-based Markov model and long-term extrapolation using partitioned survival modeling data assuming adults with LN start with active disease, transitioning to complete or partial renal response, kidney failure, or death. In the current analysis, clinical data for voclosporin, duration of voclosporin treatment for nonresponders, and drug costs reflecting the 2023 price of voclosporin were updated. Additionally, health care payer costs of disease management were incorporated based on real-world claims data on the costs of treating patients with LN. Using the LN CEM with inputs reflecting the latest and most relevant evidence, the incremental cost of voclosporin per QALY was $88,076 and per evLYG was $77,643. For a subpopulation of Black, Hispanic, and Latino patients, the incremental cost of voclosporin per QALY was $77,435 and per evLYG was $67,828. Following the inclusion of updated data in the cost-effectiveness analysis, voclosporin remains a cost-effective therapy for the treatment of active LN including in a Black, Hispanic, and Latino subpopulation, substantially below the ICER willingness-to-pay threshold of $150,000/QALY.

CCR10 Deficiency Reduces Blood Pressure Elevations, End-Organ Damage, and Cutaneous Infiltration of Regulatory T Cells in a Murine Model of Hypertension

Emerging evidence suggests a key role for inflammation and immune cell activation in the pathogenesis of hypertension and its associated end-organ damage. Regulatory T cells (Tregs) function primarily to limit inflammation and are generally considered protective in hypertension. However, Treg subsets can also have tissue-specific functions and play pathogenic roles in some inflammatory diseases through mechanisms, such as limiting angiogenesis. As such, the role of Tregs and its subsets in hypertension remain unclear. Recently, we demonstrated that CCR10+ Tregs are selectively decreased in the circulation of hypertensive patients. CCR10 is a key chemokine receptor for recruitment of immune cells to the skin. Although the skin has not been well studied in hypertension, prior reports in humans demonstrate that loss of skin microvessels (microvascular rarefaction) is a putative mechanism for blood pressure (BP) elevations in hypertension. Recent evidence also suggests that Tregs can promote apoptosis of vascular smooth muscle cells and endothelial cells (ECs). Thus, we hypothesized that CCR10+ Tregs promote hypertension through skin infiltration leading to enhanced microvascular rarefaction. Herein, we demonstrate that, compared to normotensive littermates, male mice with angiotensin II (Ang II)-induced hypertension have selectively increased abundance of CCR10+ Tregs in the skin (p=0.0004) with a corresponding decrease in the circulation (p=0.003). These mice also displayed increased cutaneous levels of the CCR10 ligand CCL27 (p=0.0007), suggesting a mechanism for increased CCR10+ Treg infiltration. To test a causal role of CCR10 in hypertension, we infused Ang II in control CCR10+/+ or CCR10-deficient (CCR10−/−) mice for 4 weeks. Our results demonstrate that CCR10−/− mice exhibit significant reductions in systolic blood pressure (p=0.004), albuminuria (p=0.01), and cardiac fibrosis (p=0.04) compared to wild type mice after Ang II infusion. In addition, CCR10−/− mice had a selective decrease in Tregs in the skin (p=0.02) without change in abundance of conventional CD4+ or CD8+ T cells after Ang II. CCR10−/− mice also exhibited greater cutaneous arteriolar density (p=0.02) after Ang II, consistent with reduced skin microvascular rarefaction. Finally, using PrediXcan, we demonstrate that higher genetically predicted levels of CCR10 are associated with increased risk of hypertension in humans. Taken together, our data suggest that CCR10 promotes Ang II-induced BP elevations and associated end-organ injury, at least in part by promoting Treg recruitment to the skin leading to microvascular rarefaction. K08HL153786, 5T32HL144446-05. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mildronate ameliorates kidney injury and reduces inflammation in Sickle Cell Disease mice

INTRODUCTION: Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and chronic inflammation that affects multiple organs including kidney, liver, brain, spleen, and heart. Renal disease, the most common complication in SCD, is a progressive disease that begins in childhood as glomerular hyperfiltration, then advances to albuminuria, following by a fast decline in glomerular filtration. It may further progress to a renal failure in adults. More than 50% of SCD patients develop chronic kidney disease (CKD), and 14-18% progress to the end-stage kidney disease. Renal injury in SCD results from a cascade of events starting with chronic red blood cells sickling and hemolysis leading to increased blood viscosity, microvascular obstruction and dilation, hypoxia in the medulla, oxidative stress, and inflammation. Mildronate (meldonium) is an anti-ischemic and anti-inflammatory medication approved in Eastern Europe. HYPOTHESIS: We hypothesized that mildronate administration reduces renal medullary hypoxia and decreases oxidative stress and inflammation ameliorating renal injury in SCD mice. METHODS: The study was approved by the Howard University IACUC. Townes SCD mice, expressing human HbS, and control mice, expressing human HbA, were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood was collected and used for hematological parameters analysis. Cytokines were measured by Bio-Plex suspension array in plasma. Hypoxyprobe Biotin kit (Hypoxyprobe Inc) was used for visualization of organ hypoxia. The effect of Mildronate on systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). Urinary KIM-1 was measured by TIM-1/KIM-1 ELISA kit (R&amp;D Systems). RESULTS: Mildornate injections did not affect hematological parameters of SCD mice including hematocrit, MCV, MCH, CMCH, erythrocytes and hemoglobin. Mildronate administration resulted in a significant reduction of the circulating pro-inflammatory cytokines IFN-γ, IL-1β and TNF-α and a trend toward reduction of IL-6, and IL-17 in SCD mice. We found higher level of hypoxia in the medulla of SCD mice compared to control mice. Mildronate injections did not reduced hypoxia in renal medulla of SCD mice. Also, mildronate injections did not change MDA levels in plasma or kidney of SCD mice. We found a significant reduction of proteinuria in SCD mice injected with mildronate compared to SCD mice injected with vehicle. Analysis of H&amp;E-stained kidneys showed significant reduction of glomerular size and medullar congestion areas in the mildronate injected SCD mice. Urinary KIM-1 levels were reduced by mildronate administration. CONCLUSIONS: Our results demonstrate that mildronate ameliorates glomerular and tubular injury in SCD mice and reduces capillary congestion. Mildronate improves renal function, in part by reducing inflammation but not through the reduction of hypoxia or oxidative stress. In future, we plan to assess the mildronate’s impact on kidney function and vessel inflammation. This work was supported by NIH grants R01HL125005, U54MD007597, and SC1HL150685. We thank Xiaomei Niu for helping with the Bio-Plex assay. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety

Rationale and ObjectiveSparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. Study DesignPatients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. Setting and ParticipantsPatients with FSGS, excluding secondary FSGS. InterventionSparsentan (200, 400, and 800mg/day). OutcomesUrine protein/creatinine ratio (UP/C), FSGS partial remission endpoint (UP/C≤1.5g/g and >40% reduction from baseline), eGFR, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years. Results109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95%CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of eGFR decline over the entire treatment period (-2.70 vs -6.56, P=0.03) and in the first 2 years (-1.69 vs -6.46, P=0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths. LimitationsThe open-label extension does not include a comparison group. ConclusionsLong-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

Advancements in immunotherapy for glomerulonephritis: Promising treatments on the horizon.

Madam, Over the years, glomerulonephritis management has been predominantly reliant on corticosteroids and immunosuppressive agents. However, emerging research on targeted immunotherapies, such as biologics and monoclonal antibodies, has shown remarkable potential in halting the disease progression and promoting remission in certain glomerular disorders [1]. Glomerulonephritis, characterised by the inflammation of glomeruli, poses a significant burden on the health system of low-income countries. A study revealed that glomerulonephritis is the most common cause of end-stage renal disease in developing countries, and it affects at least 21% of the adult population in Pakistan [2]. The emergence of novel immunotherapeutic approaches may revolutionise treatment outcomes, offering new hopes for patients suffering from this complex and challenging kidney disorder in Pakistan. An extensive study assessed the role of Belimumab, a B-lymphocyte stimulator (BLyS) inhibitor, in patients with lupus nephritis. The monoclonal antibody, Belimumab showed promising outcomes in patients with lupus [3]. Another recent study revealed that rituximab, a monoclonal antibody to CD20 can be used for patients suffering from ANCA Glomerulonephritis or also in patients with steroid resistance [4]. These findings demonstrated a substantial reduction in proteinuria and in increased remission rates following rituximab therapy, highlighting its potential as a promising treatment option. According to a current study, dealing with glomerulonephritis in low-resource setting areas in Pakistan is very challenging as it's only limited to tertiary care hospitals [5]. As the landscape of glomerulonephritis management evolves, it is crucial to encourage further research and clinical trials to establish immunotherapies' long-term efficacy and safety. Collaborative efforts among nephrologists, researchers, and pharmaceutical companies can drive the development of personalized treatment strategies, optimising patient care and outcomes. In conclusion, immunotherapy for glomerulonephritis holds immense promise, with encouraging results emerging from research conducted in Pakistan and around the globe. The government should build some nephrology centres in areas devoid of tertiary settings so the patients can be treated on time. As we move toward an era of precision medicine, harnessing the potential of immunotherapeutic agents in glomerulonephritis treatment represents a beacon of hope for patients seeking effective and targeted therapies.

Comparison of Telmisartan and Verapamil in Reducing Proteinuria in Diabetic Nephropathy Patients

Background: In diabetes, complications often extend to diabetic nephropathy, marked by proteinuria. This study investigates telmisartan and verapamil's efficacy in mitigating proteinuria. Verapamil, a calcium channel blocker, dilates vessels, while telmisartan, an angiotensin II receptor blocker, induces vasodilation. However, evidence is confined to a single foreign study, prompting this research for more comprehensive insights. Objective: To comparison of telmisartan and verapamil in reducing proteinuria in diabetic nephropathy patients. Study Design: It was a prospective comparative study. Settings: Department of Medicine, DHQ Teaching Hospital, KMU Institute of Medical Sciences, Kohat. Duration: 05-02-2022 to 05-08-2022. Methods: One hundred patients with diabetic retinopathy and meeting inclusion criteria were enrolled in the study after taking informed written consents and two equal groups were made using lottery method. Patients in group A were given trandolapril 2 mg/day + telmisartan 80 mg/day whereas patients in group B were given trandolapril 2 mg/day + verapamil 120 mg/day, for three months. Study variables were noted at baseline and at three months. SPSS version 26.0 was used for data analysis. Results: Mean age of the patients was 46.20±13.80 years. Gender distribution revealed that 52.0% were male, while 48.0% were female. The duration of the disease varied among the participants, with an overall mean of 9.20±3.73 years. Mean BMI was 27.46±3.50 kg/m². MABP was recorded as 120.16±2.84 mmHg. Proteinuria, a significant parameter in this study, was observed with a mean value of 354.37±20.26 g/day. Glomerular Filtration Rate (GFR) was measured at 56.72±2.52 mL/dk. HbA1C was found to be 8.94±0.34%. Both the groups did not possess any significant difference between them at baseline (p-value&gt;0.05). After treatment, mean proteinuria level in this study was significantly less in group A than group B with p-value=0.043. Moreover, mean change in proteinuria between before and after treatment was significantly high in group A than group B (p-value=0.000). After treatment mean GFR was less in insignificantly high in group A than group B (p-value=0.450) and likewise mean change in GFR from the baseline also had insignificant difference between the groups (p-value=0.489). Post treatment, mean HbA1c and MABP were less in group A than group B but the difference was not significant (p-value&gt;0.05). Likewise, mean change also had insignificant difference between the groups. Conclusion: In conclusion, our study comparing the effects of Trandolapril with Telmisartan versus Trandolapril with Verapamil in diabetic nephropathy patients revealed a significant reduction in proteinuria in the Telmisartan group. However, no substantial differences were noted in GFR, HbA1c, and MABP between the groups. These findings provide valuable insights into optimal therapeutic strategies for managing diabetic nephropathy.