Decrease In Proteinuria Research Articles

Antiproteinuric action of amiloride in paediatric patient with corticoresistant nephrotic syndrome

IntroduccionIn nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both variables. ObjetivesEvaluate the anti-proteinuric effect of 2 non-immunological therapeutic regimens, the quantitative relationship between podocyturia and proteinuria. Material and methodsWe included children aged 4–12 years with corticoresistant nephrotic syndrome, using 2 different schemes: group A, enalapril + losartan, and group B, enalapril + losartan + amiloride. ResultsIn group A, 17 patients completed the study, the initial mean proteinuria was 39 mg/m2/h and mean proteinuria at the end was 24 mg/m2/h, while in group B 14 patients were treated and the initial average proteinuria was 36 mg/m2/h and the end average proteinuria was 13 mg/m2/h. The paired T test showed significant differences in the decrease in proteinuria, for patients in group B without variation in podocyturia. The 2 factors associated with an increase in proteinuria were podocyturia and the time elapsed from the diagnosis of cortico-resistant nephrotic syndrome to the start of treatment anti-proteinuric. ConclusionsThe use of amiloride decreased proteinuria, without significantly modifying podocyturia; we did not observe a positive relationship between both variables.

POS-455 RITUXIMAB IN MANAGEMENT OF PEDIATRIC NEPHROTIC SYNDROME

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Many studies in the past decade have reported the effectiveness of rituximab for complicated FRNS/SDNS and refractory SRNS. Prospective study 1) To evaluate the efficacy of rituximab in glomerular diseases. 2) To evaluate response of rituximab by complete or partial remission of nephrotic syndrome after two to four doses of rituximab 375mg/m2, during the follow up period of 12 months and the outcome had been assessed using blood and urine biochemistry values (UPCR/24hr urine protein,serum albumin) i.e., Complete remission (UPCR < 0.2), Partial remission (> 50% decrease in proteinuria from base line), CD 19 cells (< 5%) 3)To look for safety of rituximab. The patients included in the study will be given the dosage of rituximab as per body surface area (BSA) i.e., 375 mg/m2 two to four doses and followed up for a period of 12 months.REGIMEN: 375 mg/m2 Rituximab (2 doses for SDNS, 4 doses for SRNS) after premedication. Inclusion criteria: Patients of age groups <18 yrs were included in the study. Patients with nephrotic syndrome who had received a trial of steroids, alkylating agent and at least 6 months therapy of calcineurin inhibitor had received the novel drug Rituximab. Exclusion criteria: Patients with active focus of infection (Acute/Chronic). Serological evidence of current or past HIV/Hepatitis B/Hepatitis C infection. Known allergic reaction to rituximab. Patients/Parents not willing to give informed consent. Out of 33 patients who received rituximab 18 patients were in SRNS group and 11 were SDNS. The mean age of the patients who used rituximab in SDNS was 13.7+- 9.1 and in SRNS was 10.7+-2.9. In SDNS, FSGS contributed 61% (n=11); MCD33% (n=3) while in SDNS, MCD 72% (n=8); FSGS 27% (n=3). The mean duration of the CNI therapy for SRNS was 20.7=-17.1 months while for SDNS was 18.7+-10.2 months. In SRNS group; Complete remission (CR) was seen in 50.0% while in FSGS 18.1%; partial remission (PR) attained in 33.3% in MCD and in FSGS 27.2% and no remission for 16.6% in MCD and 54.4% in FSGS. In SDNS group, CR was seen in 75.0% in MCD and 33.3% in FSGS; PR obtained in 12.5% in MCD and 66.6% in FSGS; no remission in 12.5% in MCD.The CD19 counts at baseline were 12.6 ± 3.4% of the leukocyte count. After rituximab therapy, CD19 levels were 0.2 ± 0.1 and 0.3 ± 0.2% after two and four doses in patients with SDNS and SRNS, respectively. This study confirm the efficacy of rituximab in patients with difficult nephrotic syndrome; remission was achieved in 50.0% patients with SRNS and a 72.72% patients achieved remission in patients with SDNS. There was a trend toward better response rates in patients with steroid-resistant MCD (83.3%) compared with FSGS (45.45%).

POS-830 NEFECON FOR THE TREATMENT OF IgA NEPHROPATHY IN PATIENTS AT RISK OF PROGRESSING TO END-STAGE RENAL DISEASE: THE NEFIGARD PHASE 3 TRIAL RESULTS

Peyer’s patches located within the gut-associated lymphoid tissue have been identified as a major source of poorly O-galactosylated immunoglobulin A (IgA)1, which triggers the formation of nephritogenic immune complexes in IgA nephropathy (IgAN). The therapeutic potential of targeting Peyer’s patches in patients with IgAN was demonstrated in the Phase 2 NEFIGAN trial, which assessed the safety and efficacy of a novel targeted-release formulation of budesonide (NEFECON), designed to deliver budesonide to the Peyer’s patches in the ileum. Patients treated for 9 months with NEFECON 16 mg/day demonstrated a significant (~30%) reduction in urine protein-to-creatinine ratio (UPCR) compared with placebo, and stabilization of estimated glomerular filtration rate (eGFR). Based on these data, the Phase 3 NefIgArd trial is a two-part design: Part A evaluates proteinuria reduction as a surrogate of the effect of NEFECON on long-term kidney function preservation. NefIgArd is a randomized, double-blind, placebo-controlled clinical trial recruiting a total of 360 patients across 155 nephrology clinics in 20 countries. Patients must be aged ≥18 years with biopsy-confirmed primary IgAN, proteinuria >1 g/24 h and eGFR 35–90 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Patients are randomized on a 1:1 ratio to NEFECON 16 mg/day or placebo. The primary endpoint, based on the first 199 patients, is the percentage decrease in proteinuria (UPCR) after 9 months of treatment. The secondary objectives include the difference in kidney function between NEFECON-treated subjects and those on placebo, as measured using eGFR, and the urine albumin-to-creatinine ratio (UACR) at 9 months compared with baseline. Between September 2018 and October 2020, 657 subjects were screened. Of these, 306 patients were randomized and 199 with 9 months of follow-up were included in the efficacy analyses of Part A of the study. At 9 months, the geometric mean UPCR was reduced by 27% in the NEFECON group compared with the placebo group (p=0.0005). At 9 months, the NEFECON group provided a statistically significant 7% (3.87 mL/min/1.73m2) treatment benefit on eGFR (p=0.0029), compared with placebo. There was a similar overall incidence of adverse events in the two treatment groups. The NefIgArd study met its primary endpoint and demonstrated a favorable safety profile. These results are indicative of a clinically meaningful reduced risk of future progression to end-stage renal disease in patients with IgAN treated with NEFECON. This trial will continue in order to validate UPCR reduction as a surrogate of long-term renal function preservation.

POS-799 EFFECT OF DARATUMUMAB/BORTEZOMIB/CYCLOPHOSPHAMIDE/DEXAMETHASONE ON RENAL FUNCTION AND HRQOL IN PATIENTS WITH NEWLY-DIAGNOSED AL AMYLOIDOSIS WITH RENAL INVOLVEMENT: RESULTS FROM THE PHASE 3 ANDROMEDA STUDY

Systemic light chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys; the extent of organ involvement impacts clinical outcomes. There are currently no approved treatments for AL amyloidosis. Although treatments for multiple myeloma (MM), including bortezomib, cyclophosphamide, and dexamethasone (VCd), have been shown to improve outcomes, more effective therapies are needed. Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as monotherapy and in combination with other agents for the treatment of MM. In the phase 3 open-label ANDROMEDA trial (NCT03201965), patients with newly diagnosed AL amyloidosis treated with DARA subcutaneous (DARA SC) + VCd (DARA-VCd) had improved objective hematologic and organ response rates over 6 cycles of treatment. Here, we present change in renal function and patient-reported outcomes (PROs) in patients with baseline (BL) renal involvement from ANDROMEDA. Patients (N=388) with newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, estimated glomerular filtration rate (eGFR) ≥20 mL/min, and absence of symptomatic MM were randomized 1:1 to DARA-VCd or VCd for 6 28-day cycles; thereafter, patients in the DARA-VCd group received DARA SC alone every 4 weeks up to 24 cycles. The percentage of patients with renal improvement (≥30% decrease in proteinuria or drop in proteinuria below 0.5g/24 hour in the absence of ≥25% decrease in eGFR) was also determined. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) improvement in global health status (GHS) and fatigue scale scores were secondary study endpoints. Here we report PRO results for Cycles 1–6 (assessed on Day 1 of each cycle). Analyses were performed in the subset of patients with renal involvement, defined as 24-hour urine protein >0.5g/day, predominantly albumin. Change from BL at various time points was analyzed using a mixed-effects model with repeated measures with patients as a random effect, and BL value, treatment group, time (weeks), and treatment-by-time interaction as fixed effects. For selected single items of the EORTC QLQ-C30, the distribution of responses and the number and percentage of patients with ≥1-point improvement from BL were summarized at each time point. Of the total population in ANDROMEDA, 115 and 114 patients in the DARA-VCd and VCd groups had renal involvement, respectively; 117 and 113 patients were evaluable for renal response. At 6 months, 53.8% of DARA-VCd and 27.4% of VCd patients had a renal response (P<0.0001). GHS (Figure) and fatigue scores remained stable with DARA-VCd but worsened with VCd by Cycle 3; the greatest between-group differences were observed at Cycle 5. At BL, 56–85% of patients reported shortness of breath, feeling weak or tired by ‘a little’ or more (Table). More DARA-VCd than VCd patients experienced ≥1-point improvements in these symptoms (Table). DARA-VCd increased renal response, with results suggestive of improvement in fatigue-related parameters, such as shortness of breath, feeling tired, or weak, in AL amyloidosis patients with renal involvement.

Subclinical and Clinical Hypothyroidism in Proteinuric Nephropathies: Amelioration of Proteinuria and Preservation of Renal Function by Thyroid Hormone Replacement Therapy

Background: Emerging evidence shows a bi-directional talk between the kidney and thyroid; yet to date, sparse data exist as to the screening and treatment of hypothyroid states, whether Subclinical Hypothyroidism (SCH) or Clinical Hypothyroidism (CHT), in Chronic Kidney Disease (CKD) patients. Objectives: The aim of the current study was to examine the association between thyroid hypofunction (whether subclinical or clinical) and proteinuric CKD (low eGFR and/or proteinuria), and to assess the impact of treating thyroid hypofunction on the progression of CKD. Patients and methods: We conducted a prospective cohort study on 100 participants with baseline proteinuric CKD who were subcategorized according to their thyroid status into three groups: 20 euthyroid, 40 (SCH), 40 (CHT). All subjects were then followed up for 2 years after receiving Thyroid Hormone Replacement Therapy (THRT) according to their thyroid status. Results: At baseline, we found a highly statistically significant association between SCH/CHT and low eGFR and proteinuria (P-value 0.001 for both) in univariate and multivariate analyses. After THRT, we found a statistically significant reduction in CKD progression as evidenced by preservation of mean eGFR and decrease in proteinuria in both groups with SCH and CHT (P-value 0.001 and 0.016 respectively) after the first 6 months of treatment that persisted over the remainder of 2-year follow-up period at a P-value 0.001. Conclusion: The current study demonstrated a strong association between baseline proteinuric CKD and hypothyroid states and showed that THRT significantly halted CKD progression in hypothyroid patients who achieved euthyroid state.

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever

Introduction and objectivesCanakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. Materials and methodsAdult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. ResultsA total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. ConclusionsCanakinumab, an IL-1 blocking agent, is not effective in decreasing proteinuria in FMF patients with already impaired renal functions and should be started early in the course of disease to prevent renal impairment.

Acción antiproteinúrica del amiloride en el paciente pediátrico con síndrome nefrótico corticorresistente

IntroduccionIn nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both variables. ObjetivesEvaluate the anti-proteinuric effect of 2 non-immunological therapeutic regimens, the quantitative relationship between podocyturia and proteinuria. Material and methodsWe included children aged 4 to 12 years with corticoresistant nephrotic syndrome, using 2 different schemes: group A, enalapril+losartan, and group B, enalapril+losartan+amiloride. ResultsIn group A, 17 patients completed the study, the initial mean proteinuria was 39mg/m2/h and mean proteinuria at the end was 24mg/m2/h, while in group B 14 patients were treated and the initial average proteinuria was 36mg/m2/h and the end average proteinuria was 13mg/m2/h. The paired T test showed significant differences in the decrease in proteinuria, for patients in group B without variation in podocyturia. The 2 factors associated with an increase in proteinuria were podocyturia and the time elapsed from the diagnosis of cortico-resistant nephrotic syndrome to the start of treatment anti-proteinuric. ConclusionsThe use of amiloride decreased proteinuria, without significantly modifying podocyturia; we did not observe a positive relationship between both variables.

Long-term safety and efficacy of hydroxychloroquine in patients with IgA nephropathy: a single-center experience.

Hydroxychloroquine (HCQ) has been used as a supportive therapy for IgA nephropathy (IgAN). We aimed to determine the long-term efficacy and safety of HCQ therapy in patients with IgAN. A total of 180 patients with IgAN who had received HCQ therapy for at least 1year were enrolled in this study. The changes in proteinuria and the estimated glomerular filtration rate (eGFR) were analyzed during the follow-up period. The level of proteinuria decreased from 1.69 [1.24, 2.30] to 1.01 [0.59, 1.74] g/day (-37.58 [-57.52, 8.24] %, P < 0.001) at 12months and to 1.00 [0.59, 1.60] g/day (-55.30 [-71.09, -3.44] %, P < 0.001) at 24months. There was no significant change in the eGFR of these patients at 12months (65.82 ± 25.22 vs. 63.93 ± 25.96ml/min/1.73m2, P = 0.411); however, the eGFR decreased from 65.82 ± 25.22 to 62.15 ± 25.81ml/min/1.73m2 at 24months (P = 0.003). The cumulative frequency of all patients with a 50% decrease in proteinuria was 72.78% at 12months. Sixty (33.3%) patients changed to corticosteroid therapy during the follow-up period. No serious adverse effects were documented during HCQ treatment. HCQ effectively and safely reduces proteinuria in IgAN patients with different levels of eGFR, supporting the maintenance of stable kidney function in the long term.

Efficacy and Safety of Immunosuppressive Monotherapy Agents for IgA Nephropathy: A Network Meta-Analysis.

Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach. Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine. Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17–1.93), MMF (RR 2.05, 95% CI 1.15–3.65), TAC (RR 3.67, 95% CI 1.06–12.63), and HCQ (RR 3.25, 95% CI 1.05–10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12–0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37–6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40–4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration. Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.

Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study.

ObjectivesCirculating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes.MethodsHere we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques.ResultsLN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months.ConclusionsAnti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN.Trial registrationThe Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

A Pilot Trial on the Effect of Levothyroxine on Proteinuria in Patients With Advanced CKD

IntroductionThyroid hormones can directly affect kidney function; elevated levels of thyroid-stimulating hormone (TSH) and chronic kidney disease (CKD) are associated with proteinuria, decreased estimated glomerular filtration rate (eGFR), and progression to end-stage renal disease. Our hypothesis is that in patients with CKD and TSH at levels considered to be in the low subclinical hypothyroidism (SCH) range, lowering TSH with levothyroxine (LVX) improves the clinical parameters of renal function.MethodsThis was a double-blind, randomized, pilot clinical trial in patients with proteinuric CKD (eGFR <60 ml/min per 1.73 m2 and proteinuria >150 mg/d) performed at the Hospital Civil de Guadalajara, with the intention of lowering TSH (levels of 1.25−2.5 μIU/l) in patients with TSH (levels of 2.6−9.9 μIU/ml with FT4 in the range of 0.7−1.8 ng/dl). Patients were randomized 1:1 to receive LVX or placebo for 12 weeks. The primary objective was to evaluate absolute levels of proteinuria at the beginning compared to the end of the study and, as a secondary objective, the changes in serum creatinine (sCr), eGFR, cholesterol, triglycerides, low-density lipoprotein (LDL), and blood pressure, and to assess the tolerability and safety of LVX.ResultsBetween March and November 2018, a total of 163 patients were assessed for eligibility; 119 patients did not meet the inclusion criteria or were excluded, and 32 patients were randomized. The demographic and clinical characteristics of the 2 study groups were essentially not different. Subjects were 66.87 (SD 12.19) years of age, 62.5% were female, 75% were diabetes mellitus, eGFR was 23.55 (±12.91) ml/min per 1.73 m2, TSH was 5.37 ± 2.13 μIU/ml, proteinuria in 24-hour urine collection was 1.52 ± 1.12, and all of them were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Proteinuria at 12 weeks in the LVX group was 0.89 SD ± 1.28 g/d, and in the placebo group it was 1.35 SD ± 0.85 g/d; when compared to placebo, LVX showed a significant decrease in proteinuria of 1.1 g/d (P = 0.0011). The eGFR in the LVX group showed an improvement of 4 ml/min/1.73 m2 (P = 0.049); in the placebo group, there was a decrease of 1.98 ml/min per 1.73 m2. The sCr, cholesterol, triglycerides, low-density lipoprotein, systolic blood pressure, and diastolic blood pressure were not different between groups. Adverse events were reported in the LVX group in 7.14% of patients and in 11.11% of patients in the placebo group; none left the study because of adverse effects, and there were no serious adverse events.ConclusionThis single-center, randomized, double-blind, placebo-controlled pilot clinical trial in patients with advanced proteinuric CKD who already used ACEIs or ARBs demonstrated that administering LVX to obtain a TSH range close to 2.5 μIU/ml decreased proteinuria and improved eGFR. Future research is needed to confirm our results and to determine whether our findings generalize to patient groups not explicitly enrolled in this small pilot trial.

Acute Kidney Injury after Administering Dapagliflozin to a Diabetic Patient with Acute Cerebral Infarction

Dapagliflozin is a recently developed oral anti-diabetic drug and SGLT2 inhibitor with well-known cardioprotective and renoprotective effects. Although a reduction of the glomerular filtration rate is induced by volume depletion and tubule-glomerular feedback during the early period after administering a SGLT2 inhibitor, the renal prognosis improves more with a decrease of proteinuria. However, the risk of acute kidney injury increases in heart failure and hypovolemia patients, and in those taking certain drugs, such as non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, or diuretics. We report acute kidney injury after dapagliflozin administration in a diabetic patient with acute cerebral infarction accompanied by right hemiplegia, motor aphasia, and dysphagia.

Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was...

Features of the course of nephropathies in combination with CAKUT-syndrome in young children

Background . Children with CAKUT-syndrome (congenital malformations of the urinary tract) quickly develop an inflammatory process, which, in combination with dysplasia and/or urodynamic disorders, creates a high risk of developing early chronic renal failure. Purpose of the study : to identify the main factors of the formation, features of the clinical course of nephropathies, morphometric parameters and features of the organ blood flow of the kidneys in young children against the background of CAKUT syndrome. Methods . Study design: It carried out a cohort prospective study. The main group included 26 children with pyelonephritis against the background of CAKUT syndrome at the age from zero to 36 months of life, the comparison group consisted of 29 children with non-obstructive pyelonephritis of the same age. It carried out a comparative analysis of antenatal and postnatal anamnesis, clinical, laboratory and instrumental data in the considered groups of children with nephro-urological pathology. Additionally, it researches the morphometric parameters of the kidneys and the Doppler indices of the renal vessels. The research conducted during 2016–2018. Results . In children with a chronic course of nephropathy in combination with CAKUT-syndrome, possible predictors of an early onset of the disease are: anemia, damage to the urinary tract with pathological urinary syndrome during pregnancy and a combination with defects of this system in the woman herself, and the development of placental insufficiency. In the group with CAKUT syndrome, a decrease in renal filtration function (in 88.5% of children) and persistent trace proteinuria (in 65.4% of children) are recorded by the end of the first year of life. According to ultrasound, in addition to signs of obstructive nephropathy, it recorded decreases in the thickness of the parenchyma and a violation of organ hemodynamics with an increase in the resistance index. In the observed group of children, CAKUT syndrome combined in 100% of cases with connective tissue dysplasia syndrome also. Conclusion . Thus, CAKUT syndrome leads to early realization of nephropathies in children with a rapid decline in renal function.

Clinical and morphological spectrum and long-term outcome in monoclonal gammopathy of renal significance: one center study

INTRODUCTION AND AIM . Monoclonal gammopathy of renal significance (MGRS), heterogeneous nosological entity, is caused by monoclonal immunoglobulin (IG) produced by a "small" B-cell lineage clone. The analysis of long-term renal prognosis in various clinical and morphological types of disease and in different degrees of hematological response (HR) in the Russian patient cohort became the goal of this study. PATIENTS AND METHODS . Patients met the criteria of MGRS (morphologically verified monoclonal IG related kidney damage, an aberrant clone in the bone marrow and/or the level of serum/urine paraprotein not met the oncohematological criteria for treatment initiation) were enrolled in this one-center prospective study from 01.01.2011 till 01.03.2020. The morphological spectrum of MGRS, types of therapy, hematological and renal responses (RR) were analyzed. HR was assessed depending on the type of monoclonal IG according to the accepted criteria. The presence of RR was considered as a decrease in daily proteinuria&gt; 30 % from the initial level or less than 0.5 g in the absence of a decrease in eGFR&gt; 25 % at the time of the end of follow-up. The progression of renal dysfunction was documented with a decrease in eGFR&gt; 25 % from baseline. Renal outcome (initiation of renal replacement therapy or eGFR &lt;15 ml/min/1.73m2 at the end of follow-up) and death were determined. Long-term renal survival was assessed by the Kaplan-Meier method. The median follow-up period was 18 (4; 38) months. RESULTS . The incidence of MGRS was 4.9 % (n = 102) of all performed kidney biopsies (n = 2042), the majority of cases represented with AL amyloidosis (AL, n = 73; 71.6 %). In cases of non-amyloid variant of MGRS (non-AL MGRS, n=29, 28.4 %) the most common types of renal injury were light chain deposition disease (27,6 %) and proliferative glomerulonephritis with deposition of monoclonal IG (27.6 %). The majority of patients (80.4 %) was treated with clone-specific agents, autologous bone marrow transplantation was performed in 13 cases. HR was achieved in 74 % and 80 % of the treated patients with AL and non-AL MGRS, respectively. RR was obtained in 42 % of patients with AL and in 62 % of patients with non-AL MGRS. The five-year cumulative renal survival did not differ significantly between the groups: 66 % in AL and 44 % in non-AL MGRS ( р =0,78). Cumulative renal survival in patients who did not achieve HR was significantly lower (42 %) than in cases with complete HR (86 %), p =0.0014. CONCLUSION . MGRS is a clinically and morphologically heterogeneous nosological entity characterized by a poor renal prognosis, especially in the absence of clone-specific therapy. Treatment in MGRS should be carried out in a timely manner with the participation of a hematologist and nephrologist in order to prevent loss of kidney function and increase life expectancy.

Adoptive Cord Blood T Regulatory Cell Therapy Leads to Resolution of Inflammation and Decreased Proteinuria in Lupus Nephritis

Background. Systemic lupus erythematosus (SLE) is associated with widespread inflammation with multi-organ involvement where renal failure is the most dreaded and fatal complication. Adoptive therapy with cord blood (CB) derived T regulatory cells has been shown to improve outcomes in disease driven by inflammation including graft versus host disease (GvHD), inflammatory bone marrow disorder, COVID-19 induced acute respiratory distress syndrome. We hypothesize that CB Treg therapy can treat lupus nephritis. Methods. The suppressive abilities of CB Tregs expressing CD4+CD25highCD127lowFoxP3+ were assayed by human cytokines assay kits (IL-10, IFN-γ, IP-10, TNF-α, IL-6, and IL-17A) in the cell culture supernatants. For examining the efficacy of CB Tregs in vivo, SLE xenograft model was created with female Rag2-/-γc-/- mice transplanted with 3x106 human SLE-peripheral blood mononuclear cells (PBMCs) by intravenous injection on day 0. The mice were allowed to develop disease and on day 30 post-transplant, they were divided into 2 groups: i) control and ii) treatment. 1x107 ex vivo-expanded, cryopreserved, allogeneic, non-HLA matchedCB Tregs were injected into SLE xenografts intravenously once per week for 4 weeks through the tail vein. Serial blood draws were performed for the phenotypic analysis, cytokine assay and anti-double stranded (ds)DNA IgG antibody analysis. Serial examination of the urine samples was performed for creatinine and albumin quantification. Histopathologic examination of the harvested organs was performed at the time of planned euthanasia at 13 weeks. Results. Co-culture of CB Tregs with the pathogenic SLE-PBMCs decreased the secretion of inflammatory cytokines including IFN-γ, IP-10, TNF-α, IL-6, and IL-17A (Figure A) with a reciprocal increase in the secretion of the anti-inflammatory IL-10 cytokine (Figure B). Adoptive therapy with CB Treg cells led to a significant decrease in circulating CD8+ effector T cells and an increase in CD4+ helper T cells (Figure C). CB Treg recipients showed preserved weight gain (Figure D), lower GvHD score (Figure E) and improved overall survival (Figure F). A significant decrease in proteinuria at 9 weeks post-transplant (Figure G) correlated with a decrease in anti-dsDNA IgG Ab levels (Figure H) and soluble CD40 ligand levels (Figure I). Histopathological results from two index cases from each arm (Figure J) demonstrated that CB Treg recipients show reduced T-cells (CD3+) (Figure K) and B-cells (CD20+) (Figure L) in the kidneys, as well as a decrease in the lymphoid infiltration into glomeruli and renal parenchyma as compared to the control arm (Figure M). Conclusion. We are the first to demonstrate the benefit of allogeneic CB Treg cell therapy for treatment of lupus nephritis. We propose to examine such a strategy in the clinical setting. Figure Disclosures Nishimoto: Janssen Pharmaceutical K.K.:: Research Funding; Bayer Yakuhin, Ltd:: Research Funding. Sadeghi:Cellenkos Inc.: Current Employment. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties, Research Funding.

Reduction Of Proteinuria In Patients With Diabetes Mellitus Type 2 With Empagliflozin Treatment

Empagliflozin belongs to the group of SGLT2 inhibitors, which are a new class of glucose lowering agents. Through their unique mechanism to reduce sodium and glucose reabsorption through the proximal tubule, SGLT2 inhibitors play an important role in the prevention and treatment of diabetic nephropathy. The study included 8 patients with type 2 diabetes mellitus on empagliflozin therapy. All of them had their first morning urine albumin/creatinine ratios examined at the beginning and at the third month of treatment. The results showed a significant decrease in albuminuria in 6 of the patients by the third month after applying empagliflozin.

Diabetic Kidney Disease Benefits from Intensive Low-Protein Diet: Updated Systematic Review and Meta-analysis.

A dietary protein intake (DPI) of between 0.6 and 0.8 g protein per kilogram body weight per day (g/kg/day) is frequently recommended for adults with moderate-to-advanced chronic kidney disease (CKD). However, evidence on whether patients with diabetic kidney disease (DKD) actually benefit from a DPI of ≤ 0.8 g/kg/day and from a low-protein diet (LPD) at CKD stages 1–3 has not been consistent. We systematically searched MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, as well as the bibliographies of articles identified in the search, for eligible randomized controlled trials that had investigated the effects of LPD (prescribed DPI < 0.8 g/kg/day) versus control diet on the progression of DKD. Nine trials that included 506 participants and follow-up periods varying from 4.5 to 60 months were included in the subsequent systematic review and meta-analysis. The data showed that patients with DKD who consumed < 0.8 g protein/kg/day had a significantly reduced decline in glomerular filtration rate (GFR) (mean difference [MD] 22.31 mL/min/1.73 m2, 95% confidence interval [CI] 17.19, 27.42; P < 0.01) and a significant decrease in proteinuria (standard mean difference [SMD] − 2.26 units, 95% CI − 2.99, − 1.52; P < 0.001) versus those on the control diet. The benefits of LPD to patients with DKD at CKD stages 1–3 were a markedly decreased proteinuria (SMD − 0.96 units, 95% CI − 1.81, − 0.11; P = 0.03) and slight but significant decreases in glycated hemoglobin (− 0.42%) and cholesterol levels (− 0.22 mmol/L). Our meta-analysis indicated that a DPI of < 0.8 g/kg/day was strongly associated with a slow decline in GFR and decreased proteinuria in the patients with DKD. Patients with CKD stages CKD 1–3 benefited from LPD in terms of a marked decrease of proteinuria and slight but significant improvements in lipid and glucose control.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00952-5) contains supplementary material, which is available to authorized users.

Mean platelet volume in children with systemic lupus erythematosus.

Platelets are heterogeneous in size, density, metabolic, functional, and biochemical properties. Mean platelet volume (MPV) is a measure of the average size of platelet in a blood sample. We aimed to evaluate the mean platelet volume as a marker for disease activity in children with systemic lupus erythematosus. This was a prospective case-control study, which included 50 patients with SLE and 50 age and sex, matched healthy controls. All subjects were subjected to history taking, physical examination and laboratory parameters in active and remission phases of the diseases. The MPV value in the SLE group was significantly higher than control group (9.6 ± 1.3 fL, 9.1 ± 0.57 fL, respectively, p = 0.04). There was a significant increase of weight, blood pressure, urea, creatinine, proteinuria, CRP, ESR, cholestrol, MPV values, SLEDAI-2K scores and significant decrease of HB, albumin, C3, mean platelet volume (MPC) in the active stage than in the remission stage. There was a significant negative correlation between MPV and MPC in active stage of the disease but the correlation was insignificant in remission stage. MPV increased in active phase of patients with SLE and can be an easy, rapid, inexpensive and simple method to assess disease activity in children with SLE.

Effective strategies for prevention of cardiovascular complications in elderly patients with arterial hypertension and obesity (clinical example)

The frequency of arterial hypertension has a clear tendency to increase with age. The presence of obesity imposes additional difficulties on the choice of antihypertensive therapy regimen due to the variety of pathophysiological mechanisms of raising blood pressure in patients with a combination of hypertension and obesity. This article presents the clinical case of a 68-year-old patient with hypertension and obesity, discusses a comprehensive approach that includes diet, regular physical activity, cognitive training and pharmacotherapy with the fixed combination of amlodipine with telmisartan and the imidazoline receptor agonist moxonidine. The choice of this combination is due to the following reasons: the ultra-prolonged action of both drugs, which allows you to control blood pressure during the day, including in the morning, when there is the greatest number of cardiovascular events; organoprotective properties; improving carbohydrate metabolism; reducing the risk of diabetes; antiatherosclerotic properties. The choice of moxonidine is due to the need of effective control of blood pressure, reduction of the activity of the sympathetic nervous system, because hypersympathicotonia is one of the central pathogenetic mechanisms for raising blood pressure in patients with hypertension and obesity, and the decrease in resting heart rate less than 80 bpm (an independent risk factor for cardiovascular complications in hypertension). Dietary recommendations will help to reduce body weight and blood pressure, slow the progression of atherosclerosis, prevent the development of cardiovascular catastrophes, and improve the quality of life. The aim of physical activity is reducing body weight, improve cognitive functions and reduce cardiovascular risks. Cognitive training will help improve cognitive function and, consequently, increase patient adherence to treatment. After six weeks of complex treatment, the patient noted the achievement of the target blood pressure, weight loss, improved mood, increased exercise tolerance, improved quality of life, as well as a decrease in proteinuria, which completely disappeared after another three months of therapy.