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. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_04_03_JASN2022060725.mp3
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.
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.
BACKGROUND AND AIMS SGLT2 inhibitors (SGLT2i) are able to decrease proteinuria and slow down eGFR decline in DKD patients. The effect is mainly obtained by increase of natriuresis and glucose-induced osmotic diuresis, resulting in a reduction in intraglomerular pressure. These hemodynamic changes are beneficial in long-term period, but up to 28% of patients treated with SGLT2i experience an acute, usually transient, eGFR reduction of more than 10% [1]. Moreover, in some case, the decrease of eGFR can be more pronounced and compromise the maintenance of therapy. High sodium and protein intake can lead to intraglomerular pressure increase and predispose to a deeper fall of eGFR. We aimed at investigating whether measured creatinine clearance (CrCl) is a more sensitive method to detect the initial dip of GFR in patients with T2D treated with SGLT2i, and if dietary sodium and protein intake can influence the extent of the early change in GFR. METHOD Subjects with type 2 diabetes (T2D) were consecutively recruited among those referring to the inpatients of combined Nephrology and Diabetology clinic in years 2020–2021. Those eligible for treatment with SGLT2i were asked to collect 24-h urinary samples for sodium and urea determination, to estimate sodium and protein intake, respectively, before and 1, 3 and 6 months after treatment initiation. RESULTS At baseline, 27 patients (M 23/F 4; age 69 ± 7 years; BMI 28.2 ± 3.6 kg/m2; HbA1c 56 ± 16 mmol/mol) had a CrCl of 83.23 ± 25.52 mL/min/1.73 m2 (eGFR 67.32 ± 16.07), which dropped by 19% at month 1 (eGFR by 6%, although not significantly) and then increased to comparable baseline values at month 6. 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) (Fig. 1). Likewise, an inverse correlation between ΔCrCl and baseline urinary urea (Fig. 2) was demonstrated at month 1 and 3 (r = −0.46; P <0.05 for both), at month 6 a similar, not significant, trend was observed (r = −0.47; P = 0.054). Proteinuria showed a significant reduction from baseline (P < 0.05); no significant relationship between change in proteinuria and urinary sodium or urea was observed. CONCLUSION The present study suggests that a higher dietary sodium and protein intake may amplify the extent of early dip in glomerular filtration rate, detected with measured CrCl, in diabetic patients undergoing SGLT2i treatment. We believe that measured creatinine clearance is a very sensitive method to detect it. Further studies are needed to confirm the results of our pilot study.
Background and Aims The risk of hospitalization and death is known to be greater among patients with chronic kidney disease. Less known are the risks after hospital discharge. Our aim is to evaluate the prognosis after hospital discharge according to the presence and the degree o CKD before the hospitalization. Method Target population: Tuscany population (patients on RRT excluded) aged 50+ years, discharged from medical setting in 2017, ordinary regimen (excluding long-term stay/ rehabilitation, trauma and hospitalizations of a special nature), without hospitalization episodes in the 28 days before, with at least one creatinine determination in an outpatient setting in 2017, prior to admission. Data were extracted from hospital discharge sheets. Exposure measurement: CKD stage, based on glomerular filtration rate estimated by CKD-EPI equation. Laboratory tests were linked with hospital data with a unique anonymous identifier. Outcome one month and one year after discharge were: - hospitalization (medical area, ordinary regime, excluding long-term stay / rehabilitation and special hospitalizations). For all causes and by diagnosis-related group. - Institutionalization or activation of home care, calculated only one year after discharge. - all-cause mortality. Statistical analysis: incidence rates (IR) and ratio of incidence rates (IRR), with 95% confidence intervals, were calculated for institutionalization / home care, hospitalization and death (rough and adjusted for covariates at discharge index: comorbidity, age, gender, discharge department, diagnosis-related group of discharge, days of hospitalization) with Poisson regression model. Results 33,253 discharges met the eligibility criteria in 2017 (28,706 subjects). The discharges of patients with a eGFR > 60 were 18,194 (54.8%), with eGFR <30 were 4,268 (12.8%). The risk of hospitalization or death increases with decreasing eGFR, both at one month and at one year. One-month death IRR for a GFR <30 vs GFR> 60 was 1.59 (CI95%: 1.39-1.83), the hospitalization IRR was 1.61 (CI95%: 1.46-1, 77). One-year death IRR was 1.46 (CI95%: 1.35-1.58), the hospitalization IRR was 1.35 (CI95%: 1.21-1.50). One-year institutionalization IRR was 1.35 (CI95%: 1.21-1.50) As expected, the main causes of hospitalization were cardiovascular, genitourinary or gastrointestinal diseases. Conclusion The lower the renal function before the hospital admission, the greater the chances of hospitalization or death, in the short term and at one year, regardless of admission diagnosis. The risk of losing autonomy also increases. For this reason, the patient discharged with known kidney disease can benefit from protected discharge paths and dedicated post-hospital follow-up.
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