Rate Of Decline In Renal Function Research Articles

Role of Blood Cell Indexes in Progresses to ESRD

AbstractChronic kidney disease (CKD) is a complex health condition characterized by the gradual loss of renal function, often leading to end-stage renal disease (ESRD). It results from a combination of medical, environmental, and genetic factors. Predicting the rate of renal function decline and effectively managing the progression to ESRD is challenging in clinical practice. CKD assessment involves various indicators, including estimated glomerular filtration rate (eGFR), albuminuria levels, serum creatinine, and others. This study aimed to explore the predictive potential of specific blood cell indexes in forecasting further renal function decline and the transition from CKD stage 3–4 to ESRD. We assessed the following blood cell indexes in 377 CKD stage 3–4 patients: absolute neutrophil count (ANC), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), derived NLR (dNLR), mean platelet volume (MPV), aggregate index of systemic inflammation (AISI), and systemic inflammation index (SII). ANC, MPV, NLR, PLR, dNLR, and SII were found to independently predict a rapid decline in eGFR. Notably, NLR and dNLR demonstrated the highest sensitivity and specificity with cut-off values of 3.36 and 2.45, respectively (NLR: 88.6 and 81.7%; dNLR: 85.2 and 75.8%). The corresponding area under the ROC curve values were 0.877 (95% CI 0.837–0.918, p < 0.001) for NLR and 0.849 (95% CI 0.805–0.892, p < 0.001) for dNLR. However, none of the blood cell indexes independently predicted the transition to ESRD. The NLR and the dNLR exhibited the highest predictive capacity towards a rapid decline in renal function in CKD. No blood cell index, however, independently predicted the transition into ERSD.

Development of a LC–MS/MS analytical method of 15 compounds related to renal function for a prognostic method of progression risk in patients with diabetic kidney disease

Diabetic kidney disease (DKD) onset and progression is a major cause of end-stage renal failure in diabetic patients, however, no practical method has been reported to predict the progression rate of renal function decline. Nine serum compounds are reported to associate with prognosis in type 1 diabetes patients; however, quantitative analytical methods for these compounds lacks. Herein, we developed a simultaneous quantitative method for 15 compounds, including Niewczas’s nine biomarker candidates, associated with renal function and its prognosis in kidney disease patients to achieve a prognostic method of renal function decline in DKD patients. This report describes the development and validation of a LC–MS/MS analytical method for 15 compounds of biomarker candidates using human plasma, serum, and urine as sample matrices. The analytes are N-acetyl-L-alanine, N6-acetyl-L-lysine, N-acetyl-L-serine, N-acetyl-L-threonine, phenyl sulfate, pseudouridine, N6-threonylcarbamoyladenosine, tryptophan 2-C-mannoside, tyrosine O-sulfate, creatinine, p-cresol sulfate, 4-ethylphenyl sulfate, indoxyl sulfate, N1-methyladenosine, and trimethylamine N-oxide. The Capcell Pak ADME-HR column was compared to several general columns and selected as the most suitable column for the simultaneous analysis of all 15 compounds. The proposed method was validated for selectivity, accuracy, precision, stability, dilution integrity, and parallelism. This report describes the suitability of the calibration ranges established and the actual sample concentrations of serum and urine from type 2 diabetic patients, as well as new findings on the unknown analyte levels of several compounds in these samples. The proposed method can be used to aid the development of prognostic methods for renal function decline in patients with DKD.

Renal dysfunction in individuals with ovarian cancer; a review on current concepts

Renal impairment is a common complication in patients with ovarian cancer. Renal impairment in ovarian cancer patients can be caused by various factors. Many of the chemotherapeutic agents administered to treat ovarian cancer are nephrotoxic and can promote kidney dysfunction, leading to renal impairment. Ovarian tumors can obstruct the urinary tract, leading to a reduction in renal function and dilation of the upper urinary tract. Acute kidney injury (AKI) can occur in ovarian cancer patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Women treated for epithelial ovarian cancer suffer an accelerated rate of renal function decline, independent of major risk factors for kidney disease. Conversely, renal impairment can affect the dosage of chemotherapy drugs used in ovarian cancer treatment. Dose reduction, dose adjustment based on pharmacokinetic data, alternative treatment regimens, and individualized dosing may be necessary to ensure optimal therapeutic outcomes while minimizing the risk of toxicity and treatment-related complications.

Chronic Kidney Disease and Accelerated Decline of Renal Function in Older Adults with HIV in Northern Thailand.

Kidney disease remains prevalent in people living with HIV even in the antiretroviral treatment era. We determine the frequency of chronic kidney disease (CKD), rate of renal function decline, and associated factors in older adults with HIV (OAHIV) aged ≥50 years in northern Thailand. We used data from the medical records and calculated the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 269 participants (58% women, 61.8 years median age), 7.1% had CKD (eGFR <60 mL/min per 1.73 m2). There were 21 OAHIV (7.8%) with >25% decline in eGFR in the past year, 90 (33%) with accelerated (>5 mL/min per 1.73 m2 per year), and 44 (16%) with rapid (>10 mL/min per 1.73 m2 per year) declining eGFR. Female gender was the only factor associated with an accelerated decline in eGFR (odds ratio, 2.307; 95% confidence interval, 1.331-3.998; p = .003). Continuous monitoring of renal function is recommended for OAHIV to guide treatment modification and intervention.

Evaluation of the Role of MSCT in the Diagnosis of Ureteral Kidney Stones

A study of 100 patients with ureteral kidney stones, in which 66 cases of kidney stones and 68 cases of ureteral stones were taken with 128 slices of computerized tomography at Hanoi Medical University Hospital from September 2019 to the end of January 2020. Results: male/female ratio was 1.7/1. The mean age was 51.2 ± 11.7. The rate of renal function decline (creatinine increase) was 18%. The supersonic, X-ray, and Multi-slice Computer Tomography (MSCT) detected stones in 89%, 84%, and 100% of cases, respectively, including 32% of kidney stones, 34% of ureteral stones, 34% of stones in both kidneys and ureters, 63.6% kidney stones in many positions. Patients with two or more stones accounted for 78.8% and the average kidney stone size was 15.5 ± 10.9 mm. Ureteral stones in the upper third accounted for 54.4%, one stone accounted for 77.9%, and the average size of ureteral stones was 9.1 ± 3.6 mm. Complications of nephrolithiasis caused by stones account for 82%, and grades II and III are the most common. Complications of ureteral dilatation due to stones accounted for 51%, perirenal fat infiltration accounted for 24% and 32% of cases of drug excretion lasted more than 1 hour. Conclusion: MSCT plays an important role in diagnosing urinary stones and assessing renal function before treatment.

Nomogram analysis of the influencing factors of rapid renal decline in patients with biopsy-proven diabetic nephropathy in type 2 diabetes.

HbA1c variability may be related to risk of poor prognoses in chronic kidney disease patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether HbA1c variability is associated with rapid renal function decline and the related risk factors in type 2 diabetic nephropathy (DN). An observational analysis was performed on 387 DN patients who were diagnosed by kidney biopsy from January 2006 through January 2016 at the Department of Nephrology, Jinling Hospital Affiliated to Nanjing University. The rapid decliners were defined as an estimated glomerular filtration rate (eGFR) decline slope ≥5 mL/min/1.73m2/year. HbA1c variability and 24 baseline clinicopathologic parameters was evaluated using the least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression. The nomogram method was applied to score the factors, and a scoring model was constructed. HbA1c variability positively correlated with the rate of renal function decline (r=0.277; p<0.001). Higher baseline eGFR, lower serum calcium concentration, glomerular lesions, arteriosclerosis, and interstitial fibrosis and tubular atrophy (IFTA) were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.811 (95% confidence interval (CI) 0.680-0.785). The proposed nomogram and score provide a useful risk estimate of fast renal function decline in patients with type 2 diabetic nephropathy.

PS-C27-7: ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY CAN PREDICT FUTURE DECLINE OF RENAL FUNCTION IN GENERAL POPULATION

Objective: Electrocardiographic left ventricular hypertrophy (LVH) has been shown to be associated with future renal function decline in patients with chronic kidney disease. However, this association remains unclear in general population. We aimed to elucidate the association between baseline LVH on electrocardiogram and future renal function decline using health checkup data. Design and method: We used a dataset derived from the annual health-screening program from 2010 to 2019. Patients with baseline estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/1.73m2 were excluded. LVH was determined by the electrocardiographic voltage criteria at baseline. Association between LVH and renal function outcomes, specifically ≧ 30% decline in eGFR from baseline, eGFR decline less than 60 ml/min/1.73m2 and 45 ml/min/1.73m2, were analyzed using multivariate Cox proportional hazard models. Results: Among total of 19,825 participants, 1,263 had LVH and 18,562 no LVH. LVH group was older and more male and current smokers, and to complicated with more hypertension, and higher systolic (136.7 ± 20.9 vs 123.7 ± 19.1 mmHg, P &lt; 0.001) and diastolic blood pressure (81.8 ± 12.6 vs 74.6 ± 12.0 mmHg, P &lt; 0.001). Baseline eGFR and HbA1c were comparable between the groups. Incidence of ≧ 30% eGFR decline was significantly higher in LVH group (P &lt; 0.001, log-rank test). LVH was associated with ≧ 30% eGFR decline (HR 1.92, 95% CI 1.26–2.91, P = 0.002) and eGFR &lt; 45 ml/min/1.73m2 (HR 3.12, 95% CI 1.54–6.35, P = 0.002) after adjustment. LVH was not associated with eGFR &lt; 60 ml/min/1.73m2 in the overall population. However, when analyzed this association in subpopulation stratified by baseline SBP (&lt; 140 and ≧ 140 mmHg), LVH was associated with eGFR &lt; 60 ml/min/1.73m2 in persons with SBP ≧ 140 mmHg (HR 1.40, 95% CI 1.10–1.79, P = 0.007) but not in those with SBP &lt; 140 mmHg (HR 0.88, 95% CI 0.68–1.14, P = 0.32) (P for interaction between LVH and baseline SBP = 0.005). Similarly, LVH was significantly associated with ≧ 30% eGFR decline and eGFR &lt; 45 ml/min/1.73m2 in persons with SBP ≧ 140 mmHg but not in those with SBP &lt; 140 mmHg, although the interaction between LVH and baseline SBP was not significant in these renal outcomes. Conclusion: Electrocardiographic LVH was independently associated with the rate of renal function decline among general population. The association between LVH and future renal function decline might be stronger in people with SBP ≧140 mmHg.

Intrarenal and Urinary Glycogen Synthase Kinase-3 Beta Levels in Diabetic and Nondiabetic Chronic Kidney Disease

Background: Renal glycogen synthase kinase-3 beta (GSK3β) overactivity has been associated with a diverse range of kidney diseases. GSK3β activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3β levels in DKD and nondiabetic chronic kidney disease (CKD). Methods: We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3β levels were measured. They were then followed for dialysis-free survival and rate of renal function decline. Results: DKD group had higher intrarenal and urinary GSK3β levels than nondiabetic CKD (p r = −0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors. Conclusion: Intrarenal and urinary GSK3β levels were increased in DKD. The intrarenal pY216-GSK3β/total GSK3β ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3β in kidney diseases deserve further studies.

A kidney resident macrophage subset is a candidate biomarker for renal cystic disease in preclinical models.

Although renal macrophages have been shown to contribute to cyst development in polycystic kidney disease (PKD) animal models, it remains unclear whether there is a specific macrophage subpopulation involved. Here, we analyzed changes in macrophage populations during renal maturation in association with cystogenesis rates in conditional Pkd2 mutant mice. We observed that CD206+ resident macrophages were minimal in a normal adult kidney but accumulated in cystic areas in adult-induced Pkd2 mutants. Using Cx3cr1 null mice, we reduced macrophage number, including CD206+ macrophages, and showed that this significantly reduced cyst severity in adult-induced Pkd2 mutant kidneys. We also found that the number of CD206+ resident macrophage-like cells increased in kidneys and in the urine from autosomal-dominant PKD (ADPKD) patients relative to the rate of renal functional decline. These data indicate a direct correlation between CD206+ resident macrophages and cyst formation, and reveal that the CD206+ resident macrophages in urine could serve as a biomarker for renal cystic disease activity in preclinical models and ADPKD patients. This article has an associated First Person interview with the first author of the paper.

Tirzepatide, A New Antidiabetic Drug with Change in the Treatment of Patients with Type 2 Diabetes

Mounjaro® (tirzepatide) was approved by the U.S. Food and Drug Administration for type 2 diabetes treatment in August 2022. Tirzepatide, a synthetic peptide consisting of 39 amino acids, is a dual GLP-1 (glucagon-like peptide-1)/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. Tirzepatide showed marked reductions in glycated hemoglobin and body weight in the SURPASS study among participants with type 2 diabetes that surpassed existing diabetes drugs. Other benefits included blood pressure reduction and lipid lowering effects. On meta-analysis and post-hoc analysis, tirzepatide did not increase the risk of major cardiovascular events and is expected to have cardiovascular benefits in future studies. In addition, it showed a protective effect on the kidney by slowing the rate of renal function decline and reducing new-onset macroalbuminuria. However, the fact that it is an injectable drug, the cost of the drug, and the high rate of gastrointestinal side effects are disadvantages to tirzepatide. Considering the superior degree of glucose reduction and weight reduction observed in tirzepatide clinical trials compared to clinical trials of other anti-diabetic drugs, we expect tirzepatide to bring about a paradigm shift in the treatment of obese type 2 diabetes patients.

Circulating Fibroblast Growth Factor-23 Levels Can Predict Rapid Kidney Function Decline in a Healthy Population: A Community-Based Study

Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD-a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades.

Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90μmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.

Blood Pressure Control in Elderly Chronic Kidney Disease Patients.

In elderly chronic kidney disease (CKD) patients, isolated systolic hypertension is common, the rate of renal function decline is slow, and there is a high possibility of physical damage due to side effects such as drug use-related orthostatic hypotension. Therefore, there are still many questions about whether lowering blood pressure in elderly patients will actually improve prognosis. Since many blood pressure-related clinical studies exclude advanced CKD and the elderly, it is particularly difficult to define target blood pressure in these populations. A randomized controlled trial is needed to establish optimal blood pressure targets and treatment strategies in elderly patients with CKD. This review seeks to summarize the guidelines available at this time.

Long-term outcomes of IgA nephropathy patients with less than 25% crescents and mild proteinuria.

Whether immunosuppressive therapy in IgA nephropathy (IgAN) patients with lessthan25% crescents (C1) and mild proteinuria can improve the renal outcome is still unclear. We recruited 140 IgAN patients with C1 and proteinuria < 1g/24h who received supportive care (n = 52) or steroid-based immunosuppressive therapy (n = 88) in Xijing Hospital from July 2008 to December 2016. The primary outcome was the rate of renal function decline. The median of proteinuria was 575.5mg/24h, the fraction of crescents was 7% (5%, 12%) and follow-up time was 69.1months. The rate of renal function decline [0.5 (- 1.5, 3.2) vs - 0.7 (- 3.5, 0.5) ml/min per 1.73 m2 per year; P = 0.01] was slower in steroid-based immunosuppressive therapy group than supportive care group. Multivariate linear regression analyses showed steroid-based immunosuppressive therapy significantly slowed down the rate of renal function decline (β = - 0.220, 95% CI - 3.804 to - 0.449, P = 0.013) after adjusting age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, the fraction of crescents and RASB. In the matched cohort, the rate of renal function decline was also slower in steroid-based immunosuppressive therapy group. The incidence of adverse events was similar between the two groups. Steroid-based immunosuppressive therapy may slow down the rate of renal function decline of IgAN patients with C1 and proteinuria ≤ 1g/24h.

No Significant Changes of Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Kidney Disease by Switching from Linagliptin to Teneligliptin.

PurposeWe compared the efficacy of teneligliptin versus linagliptin for glycemic control and renoprotection in patients with advanced-stage diabetic kidney disease.Patients and MethodsChanges in the glycated hemoglobin (HbA1c), fasting blood glucose concentration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) during a 12-month period were retrospectively analyzed after switching from linagliptin to teneligliptin in 13 patients with advanced-stage diabetic kidney disease (teneligliptin group). Thirteen propensity score-matched patients who were treated with linagliptin alone served as controls (linagliptin group).ResultsThe HbA1c, fasting blood glucose concentration, and UACR did not change during the 12-month study period in either group. The annual change rate in the eGFR did not differ between before and after baseline in either group.ConclusionSwitching from linagliptin to teneligliptin may not improve glycemic control, reduce urinary protein excretion, or ameliorate the rate of renal function decline in patients with advanced-stage diabetic kidney disease. These results suggest that teneligliptin may not be more advantageous for glycemic control and renoprotection compared with linagliptin in patients with advanced-stage diabetic kidney disease.

Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy.

BackgroundAccelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN. MethodsWe included a retrospective cohort of 105 patients with biopsy-proven IgAN. Tubular DcR2 expression was assessed at renal biopsy and the Oxford histological MEST-C score [mesangial hypercellularity (M), endocapillary proliferation (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C)] defined disease severity. IgAN progression was defined as a composite of end-stage renal disease or a 30% decline in the estimated glomerular filtration rate (eGFR), analyzed using Kaplan–Meier and Cox regression analyses. ResultsTubular DcR2 was overexpressed in IgAN. Numbers of DcR2 and p16 double-positive RTECs increased with increasing severity of tubular atrophy/interstitial fibrosis (T lesion). Patients with ≥25% tubular DcR2 expression experienced worse proteinuria, T lesions and a lower eGFR. Cumulative renal survival was significantly lower in patients with ≥25% DcR2 positivity. Multivariate regression analyses showed that ≥25% tubular DcR2 expression was significantly associated with worse eGFR slopes (the rate of renal function decline; P = 0.003) and the incidence of the composite outcome (P = 0.001) in IgAN. The addition of tubular DcR2 to a model with clinical data at biopsy (mean arterial pressure, proteinuria and eGFR) or MEST-C score significantly improved the 5-year risk prediction of IgAN progression, as confirmed by receiver operating characteristic curve analyses.ConclusionsTubular DcR2 expression detected at biopsy was a strong independent predictor for IgAN progression and might have prognostic value in addition to established risk markers.

Arteriolar hyalinosis is related to rapid GFR decline and long-standing GFR changes observed on renal biopsies in normo-microalbuminuric type 2 diabetic patients

Whether or not renal structural changes, especially arteriolar hyalinosis, are related to the rate of renal functional decline and increase in urinary albumin excretion (UAE) at the early stage of diabetic nephropathy in patients with type 2 diabetes is still unknown. Our previous study determined that arteriolar hyalinosis is an independent risk factor for low GFR. We sought to determine whether arteriolar hyalinosis is also a risk factor for rapidly progressive decline in GFR. We evaluated 22 type 2 diabetic patients with normo- or microalbuminuria who took part in the previous study, to clarify which renal histological factors were associated with changes in UAE and the glomerular filtration rate (GFR) during 11.0 ± 3.0 years of follow-up. Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate the glomerular and interstitial structural changes. In all 22 patients, the GFR was significantly decreased from baseline to follow-up, while the UAE did not change markedly between the 2 periods. After 11 ± 3 years of follow-up, the GFR was significantly lower in the rapid decliner group (annual rate of GFR decline ≥3.0%) than in the non-rapid decliner group (p = 0.017). The index of arteriolar hyalinosis (IAH) at baseline in the rapid decliners was significantly larger than in the non-rapid decliners (p = 0.015). The IAH showed a significant negative correlation with the GFR at follow-up (r = 0.50, p = 0.018) and the annual rate in the GFR decline (r = 0.47, p = 0.027) and significant positive correlations with UAE at follow-up (r = 0.46, p = 0.034) and the annual rate in the UAE increase (r = 0.57, p = 0.005). The GFR at follow-up in patients with IAH ≥2.0 was significantly decreased from baseline (p = 0.042) and significantly lower than that of the patients with IAH <2.0 (p = 0.026), which did not decrease significantly from baseline. The frequency of rapid decliners was larger in the IAH ≥2.0 than in the IAH <2.0 patients (p = 0.037). Aggravated arteriolar hyalinosis was a risk factor for a rapid GFR decline. This finding might reflect initial changes in early diabetic nephropathy.

A Post Hoc Analysis of Tolvaptan (TOL) Efficacy and Safety in Slowing Rate of Renal Function Decline in Subjects with Very Late-Stage Autosomal Dominant Polycystic Kidney Disease (ADPKD)

A Post Hoc Analysis of Tolvaptan (TOL) Efficacy and Safety in Slowing Rate of Renal Function Decline in Subjects with Very Late-Stage Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline

BackgroundWhile histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN.MethodsIn this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient’s kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence.ResultsProgression to ESKD was associated with worsening interstitial fibrosis score (p = 0.05), lower baseline eGFR (p = 0.02), higher ACR (p = 0.001), and faster eGFR decline (p < 0.001). The rate of eGFR decline did not associate with any histologic parameter. Baseline ACR was the only studied variable correlating with eGFR slope (rho = − 0.41).ConclusionsRenal histology predicts ultimate progression to ESKD, but not the rate of progression. Future work is required to identify novel predictors of rapid functional decline in patients with diabetic nephropathy.

Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide.

The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial. This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD. All patients were followed for a medial of 33.2months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was - 4.5 (- 12.6, - 0.1) ml/min/1.73m2peryear. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194-0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1-2), crescents present (C1-2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups. Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.