Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of chronic kidney disease. ADTKD pregnancy outcomes have not previously been described. Methods: A cross-sectional survey was sent to women from ADTKD families. Results: Information was obtained from 85 afffected women (164 term pregnancies) and 23 controls (50 pregnancies). Only 16.5% of genetically affected women knew they had ADTKD during pregnancy. Eighteen percent of ADTKD mothers had hypertension during pregnancy versus 12% in controls (p = 0.54) and >40% in comparative studies of chronic kidney disease in pregnancy. Eleven percent of births of ADTKD mothers were <37 weeks versus 0 in controls (p < 0.0001). Cesarean section occurred in 19% of pregnancies in affected women versus 38% of unaffected individuals (p = 0.06). Only 12% of babies required a neonatal intensive care unit stay. Conclusions: ADTKD pregnancies had lower rates of hypertension during pregnancy versus other forms of chronic kidney disease, which may have contributed to good maternal and fetal outcomes.

Quality of life in patients with autosomal dominant tubulointerstitial kidney disease
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AIMS: The reaction to diagnosis and quality of life (QOL) in autosomal dominant tubulointerstitial kidney disease (ADTKD) due to UMOD and MUC mutations from the time of diagnosis until treatment for end-stage kidney disease (ESKD) has not been characterized. It is unclear how asymptomatic patients react to a positive genetic test result. MATERIALS AND METHODS: A cross-sectional survey concerning QOL and genetic testing was delivered to 622 individuals who had undergone genetic testing from families with known ADTKD. RESULTS: 286 of 622 individuals completed the survey, including 61 (21%) genetically unaffected, 36 (12%) with stage 1, 2 chronic kidney disease (CKD), 51 (18%) stage 3, 41 (14%) stage 4 pre-dialysis, 50 (17%) receiving dialysis, and 47 (16%) s/p kidney transplantation. Of 55 respondents who thought they had normal kidney function at the time of testing and were found to have ADTKD, 51 (93%) were happy testing was performed, 3 (5%) neutral, and 1 (2%) neutral/unhappy. 42 of 183 (23%) affected individuals stated that ADTKD "has a substantial effect and I think about it daily," 47 (26%) think about ADTKD weekly, 48 (26%) monthly, and 48 (26%) less than monthly. The mean PROMIS anxiety score was similar between unaffected and affected individuals and the general population. Depression was present in 41% of affected vs. 23% of unaffected individuals (p = 0.01). CONCLUSION: Genetic testing of presymptomatic patients for ADTKD is reasonable when requested. This study provides reassurance regarding the impact on QOL of the increased use of genetic testing to diagnose kidney disease. ADTKD has a significant impact on QOL, with depression, not anxiety, being more prevalent in affected individuals.

Temporal trends in fluid management with incremental hemodialysis
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BACKGROUND: Incremental hemodialysis (HD) is seldom prescribed in the United States. This study describes longitudinal changes in volume management in patients with incident end-stage kidney disease (ESKD) initiated on bi-weekly (twice a week) HD, later converted to thrice-weekly HD. MATERIALS AND METHODS: 23 patients (mean age 65.6 years, 48% male, and 30% black) were included. Repeated measurement analysis of regression was used to test for differences in interdialytic weight gain (IDWG) and ultrafiltration rate (UFR) over three dialysis periods: the first 3 months of bi-weekly HD, the last 3 months of bi-weekly HD, and the first 3 months of thrice-weekly HD. RESULTS: The mean transition time to thrice-weekly HD was 332.9 days. Compared to the first 3 months of HD, the IDWG and UFR increased by 0.6 kg and 2.2 mL/kg/h in the last 3 months of bi-weekly HD (p = 0.02 and 0.009, respectively) and by 0.7 kg and 2.1 mL/kg/h in the first 3 months of thrice-weekly HD (p = 0.002). The average proportion of patients with IDWG > 5.7% of the dry weight was 0% in the first 3 months of bi-weekly HD, 12% in the last 3 months of bi-weekly HD, and 4% in the first 3 months of thrice-weekly HD; while the average proportion of patients with UFR > 10 mL/kg/h was 16%, 39%, and 25%, respectively. CONCLUSION: Fluid management in incident-ESKD patients receiving bi-weekly HD deteriorates prior to conversion to thrice-weekly HD. Further studies are needed to optimize the prescription of incremental HD.

A Single-Center Retrospective Study of Acute Kidney Injury Incidence in Patients With Advanced Malignancies Treated With Antimitochondrial Targeted Drug.

INTRODUCTION: Mitochondrial dysfunction plays an important role in the pathophysiology of kidney disease. Inhibitors of mitochondrial metabolism are being developed for the treatment of solid organ and hematologic malignancies. We describe the incidence and clinical features of acute kidney injury (AKI) in patients treated with the antimitochondrial drug CPI-613. METHODS: We identified 33 patients with relapsed or refractory malignancy, previously enrolled in 3 open-label phase II studies, who received single-agent CPI-613 chemotherapy. AKI was defined by the Kidney Disease Improving Global Outcomes serum creatinine criteria. Participants were followed for a median (25th-75th percentile) of 120.0 (74.0-301.0) days. Risk factors for AKI were assessed by proportional hazards regression using univariate and multivariate analyses. RESULTS: Participants had baseline mean (SD) age of 63.8 (11.6) years and serum creatinine 0.9 (0.3) mg/dl. AKI developed in 9 (27%) patients; chart review failed to identify a potential cause of AKI other than CPI-613 administration in 5 (15%) patients, of whom 1 had AKI stage 1, 1 had AKI stage 2, and 3 experienced AKI stage 3. Time from initiation of CPI-613 treatment to AKI was 51.0 (16.0-58.0) days. Age, per 5-year increase, was associated with higher risk of AKI (adjusted hazard ratio 2.01, 95% confidence interval 1.06-3.79, P = 0.03). Follow-up serum creatinine was available in 4 participants 174.8 (139.6) days after the episode of AKI; 3 patients had complete recovery in kidney function and 1 had partial recovery. CONCLUSION: AKI is a possible complication during treatment with mitochondria-targeted chemotherapy.

The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial.

BACKGROUND: Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. STUDY DESIGN: 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. SETTING & PARTICIPANTS: Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. INTERVENTION: 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). OUTCOMES: Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. MEASUREMENTS: Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. RESULTS: There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25 mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. LIMITATIONS: Open-label study, few peritoneal dialysis patients. CONCLUSIONS: Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.