Effects of Dietary Sodium and Protein Intake on Glomerular Filtration Rate in Subjects with Type 2 Diabetes Treated with Sodium-Glucose Cotransporter 2 Inhibitors.

BACKGROUND: Approximately one-fourth of patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) experience an acute estimated glomerular filtration rate (eGFR) reduction of more than 10% ("dippers"). High sodium and protein intake can increase intraglomerular pressure and predispose to a decline in renal function. We investigated whether measured creatinine clearance (CrCl) is a sensitive enough method to detect the initial dip of GFR and if dietary sodium and protein intake might influence the extent of the early change in GFR. METHODS: 28 subjects with type 2 diabetes (T2D) were enrolled. For sodium and urea determination, 24-h urinary samples were collected to estimate sodium and protein intake respectively before and 1, 3 and 6 months after SGLT2i initiation. RESULTS: Mean CrCl was 83.23±25.52 mL/min/1.73 m2 (eGFR 67.32±16.07) and dropped by 19% at month 1 (eGFR by 6%). Dippers were 64 and 40%, according to CrCl and eGFR, respectively. Exploring the potential correlation between changes in renal function and salt intake, ΔCrCl and baseline urinary sodium were inversely related at month 1 (r=-0,61; p<0.01), at month 3 (r=-0.51; p=0.01) and month 6 (r=-0,48; p<0.05). Likewise, an inverse correlation between ΔCrCl and baseline urinary urea was demonstrated at months 1 and 3 (r=-0.46; p<0.05 for both); at month 6, a similar trend was observed (r=-0.47; p=0.054). CONCLUSIONS: The present study suggests that a higher dietary sodium and protein intake may amplify the extent of the early dip in GFR, as detected with measured CrCl, in diabetic patients undergoing SGLT2i treatment.

A Clinical Workflow for Cost-Saving High-Rate Diagnosis of Genetic Kidney Diseases.

SIGNIFICANCE STATEMENT: To optimize the diagnosis of genetic kidney disorders in a cost-effective manner, we developed a workflow based on referral criteria for in-person evaluation at a tertiary center, whole-exome sequencing, reverse phenotyping, and multidisciplinary board analysis. This workflow reached a diagnostic rate of 67%, with 48% confirming and 19% modifying the suspected clinical diagnosis. We obtained a genetic diagnosis in 64% of children and 70% of adults. A modeled cost analysis demonstrated that early genetic testing saves 20% of costs per patient. Real cost analysis on a representative sample of 66 patients demonstrated an actual cost reduction of 41%. This workflow demonstrates feasibility, performance, and economic effect for the diagnosis of genetic kidney diseases in a real-world setting. BACKGROUND: Whole-exome sequencing (WES) increases the diagnostic rate of genetic kidney disorders, but accessibility, interpretation of results, and costs limit use in daily practice. METHODS: Univariable analysis of a historical cohort of 392 patients who underwent WES for kidney diseases showed that resistance to treatments, familial history of kidney disease, extrarenal involvement, congenital abnormalities of the kidney and urinary tract and CKD stage ≥G2, two or more cysts per kidney on ultrasound, persistent hyperechoic kidneys or nephrocalcinosis on ultrasound, and persistent metabolic abnormalities were most predictive for genetic diagnosis. We prospectively applied these criteria to select patients in a network of nephrology centers, followed by centralized genetic diagnosis by WES, reverse phenotyping, and multidisciplinary board discussion. RESULTS: We applied this multistep workflow to 476 patients with eight clinical categories (podocytopathies, collagenopathies, CKD of unknown origin, tubulopathies, ciliopathies, congenital anomalies of the kidney and urinary tract, syndromic CKD, metabolic kidney disorders), obtaining genetic diagnosis for 319 of 476 patients (67.0%) (95% in 21 patients with disease onset during the fetal period or at birth, 64% in 298 pediatric patients, and 70% in 156 adult patients). The suspected clinical diagnosis was confirmed in 48% of the 476 patients and modified in 19%. A modeled cost analysis showed that application of this workflow saved 20% of costs per patient when performed at the beginning of the diagnostic process. Real cost analysis of 66 patients randomly selected from all categories showed actual cost reduction of 41%. CONCLUSIONS: A diagnostic workflow for genetic kidney diseases that includes WES is cost-saving, especially if implemented early, and is feasible in a real-world setting.

Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience.

BACKGROUND: Autoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay. METHODS: The purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment. RESULTS: According to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance. CONCLUSION: Depending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.

Different outcomes of atherosclerotic renal artery stenosis managed with stenting: results from a cohort study.

BACKGROUND: To determine whether the type of renal artery stenosis and the rapid decline of renal function may have an impact on renal outcome after stenting. METHODS: Thirty patients with chronic kidney disease stages 3-4 and renal artery stenosis underwent stenting. The mean follow-up was 33 months; the change of estimated glomerular filtration rate was expressed as negative or positive value in mL/mo (ΔGFR). We identified two types of subgroups, on the basis of stenosis type: 1 (unilateral) N = 13 and 2 (7 bilateral, 2 single kidney, 8 prevalent kidney) N = 17; on the basis of declining ΔGFR in a pre-stenting period of 10 months: slow progressor (N = 11) and fast progressor (N = 13). RESULTS: Thirty-seven stents were placed successfully. After stenting the median ΔGFR value was significantly greater in subgroup 2 compared with subgroup 1 (0.02 vs. -0.16; p = 0.02). Being in fast progressor and in subgroup 2 were associated with improved renal function after stenting (8 of 13 patients, p = 0.013; 11 of 17 patients, p = 0.032). In a logistic regression the only significant relationship is between improvement of renal function and rapid decline of pre-stenting GFR (odds ratio 16; p = 0.005). CONCLUSION: The predictable benefit from renal stenting may be most likely in patients presenting with a rapid decline of GFR associated with renal artery stenosis affecting the whole renal mass that is both kidneys or single functioning kidney.