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.

Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.

[Geriatric nephrology: an overview]. / Nefrologia geriatrica: an overview.

INTRODUCTION: Chronic kidney disease (CKD) is a highly prevalent condition and its prevalence is increasing worldwide, particularly in adults aged 70 years. Epidemiological studies showed that as many as 2054% of the older adults suffer from CKD in stages 3-5. Nevertheless the question whether this lower eGFR is a consequence of kidney disease or if it is the result of a physiological aging is still debated, even if it implies a reduced renal reserve and vulnerability to drugs overdose with increased risk of acute kidney injury (AKI). MATERIALS AND METHODS: PubMed search was conducted for available English literature, describing the actual knowledge about specific and frequent issues reported in the acute and chronic kidney disease in older adults. Prospective and retrospective studies, as well as meta-analyses and latest systematic reviews were included. RESULTS: Most of the studies examined and reviewed were discarded for wrong population or intervention or deemed unfit. Only 103 met the inclusion criteria for the review. The studies included in the review were grouped into two areas: chronic and acute kidney disease in older adults and we have analysed the peculiar and frequently found issues in this population. CONCLUSIONS: The geriatric population is increasing worldwide. We should consider peculiar aspects of this population, such as sarcopenia, malnutrition, psychological and cognitive deficits and increased risk of AKI, in order to reach a good quality of life, with improved doctor / patient relationship, a greater adherence to therapy, a reduction in health care costs, and if possible, adequate "end of life", as far as it is approved by the patient and his family. The achievement of these objectives requires an organized work in multidisciplinary teams that evaluate overall the geriatric patient.

Biological dynamics of hepatitis B virus load in dialysis population.

BACKGROUND: Control of the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major advances in the management of end-stage renal disease. However, the natural history of HBV in dialysis patients remains unclear. The aim of this study is to measure monthly HBV viral load (HBV DNA) in a large cohort (n = 29) of hepatitis B surface antigen (HBsAg)-positive chronic dialysis patients during 12 months. METHODS: HBV DNA was measured using the Amplicor HBV Monitor Test (Roche Diagnostics, Branchburg, NJ), an in vitro assay using polymerase chain reaction nucleic acid amplification and DNA hybridization for the quantitative measurement of HBV DNA in serum. RESULTS: We observed three HBV DNA patterns: (1) patients persistently positive by Amplicor HBV Monitor Test (persistent HBV DNA; 7 of 29 patients; 24.1%), (2) individuals with alternatively positive and negative results (intermittent HBV DNA; 18 of 29 patients; 62.1%), and (3) patients persistently negative by Amplicor HBV Monitor Test (4 of 29 patients; 13.8%). HBV viral load was greater in patients with persistent compared with intermittent HBV DNA (persistently HBV DNA positive; 2.686 x 10(4) copies/mL; 95% confidence interval [CI], 5.2499 x 10(4) to 1.8158 x 10(4)copies/mL) versus intermittently HBV DNA positive (1.071 x 10(3) copies/mL; 95% CI, 8.524 x 10(3) to 4.09 x 10(2) copies/mL; P = 0.0001). In the entire group, HBV load at study entry was low and did not change versus the end of follow-up. CONCLUSION: Three patterns of HBV viremia in dialysis patients over time were assessed; HBV load was not high and was relatively stable. HBsAg-positive patients who were intermittently HBV DNA positive had less HBV viral load than persistently HBV DNA-positive patients. Periodic testing for HBV DNA to assess the virological status of HBsAg-positive dialysis patients is recommended.