Knebelmann, Bertrand

Abstract Background Pain is the highest prioritized patient-reported outcome in people with autosomal dominant polycystic kidney disease (ADPKD) but remains infrequently and inconsistently measured in clinical trials and poorly managed in clinical settings. A recently completed systematic review of pain in ADPKD identified 26 different outcome measures. None of these measures were considered appropriate as a core outcome measure due to the lack of patient-important dimensions, inadequate content, relatively long duration of completion time and limited evidence to support psychometric robustness. Methods We convened an international Standardized Outcomes in Nephrology–Polycystic Kidney Disease consensus workshop involving 21 patients/caregivers and 40 health professionals (clinicians, nurses, researchers, policy makers and industry representatives) from 18 countries to discuss the identification or development of a core outcome measure for pain. Results Four themes were identified highlighting fundamental issues for the measurement of pain in ADPKD: distressing and disrupting life participation; variability and ambiguity in defining pain; stigma, frustration and adaptation to pain; and ensuring validity and feasibility of pain measures. Conclusions Existing measures were found to be insufficient in capturing pain as a core outcome and there was consensus on the need for a new validated measure that is simple, succinct and addresses the impact of pain on life participation. This measure will facilitate the appropriate prioritization of pain in all trials and guide clinical decision making in people with ADPKD.

Abstract Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

Background. Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD) which is characterized by 2,8-dihydroxyadenine renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients. Methods. Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France. The CKD-EPI and CKiD equations were used to calculate glomerular filtration rate estimates. Allograft survival was analyzed employing the Kaplan-Meier method. The Wilcoxon-Mann-Whitney test was used to compare alllograft outcomes according to xanthine oxidoreductase (XOR) inhibitor treatment status at transplantation. Results. Seventeen patients (9 females) received 22 kidney transplants. Age at first transplantation was 47.2 (14.9–67.0) years. Ten patients received XOR inhibitor therapy pretransplant (11 allografts), while 8 patients did not receive such treatment before transplantation (11 allografts). Two-year allograft survival was 91% and 55% in the 2 groups, respectively (P = 0.16). The median (range) estimated glomerular filtration rate at 2 years posttransplant was 61.3 (24.0–90.0) mL/min/1.73 m2 when XOR inhibitor therapy was initiated before transplantation, and 16.2 (10.0–39.0) mL/min/1.73 m2 (P = 0.009) when such treatment was not administered pretransplant. Conclusions. Kidney allograft outcomes are good in APRT deficiency patients beginning XOR inhibitor therapy pretransplant. Delay in such treatment is a major cause of premature graft loss in these patients. Increased awareness among clinicians is imperative, promoting early diagnosis of APRT deficiency and pharmacotherapy initiation before kidney transplantation.