Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review

Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy

Hypokalemia Duration in the First Year Associated with Subsequent Peritoneal Dialysis-Associated Peritonitis: A Multicenter Retrospective Cohort Study

Background: The association of hypokalemia (LK) with peritoneal dialysis-associated peritonitis (PDAP) risk remains uncertain. Here, we calculated LK duration in the first PD year and evaluated its association with PDAP. Methods: A multicenter, retrospective, incident cohort study of 1633 participants was conducted from January 2008 to October 2020 in China. The duration of LK and severe hypokalemia (SLK) was calculated as the total number of months that a patient’s serum potassium (SK) level was less than 3.5 or 3.0 mEq/L during the first PD year. The study outcome was the risk of subsequent PDAP started in the second year and later. Cox proportional hazards models and competing risk models were used to assess the association. Results: The subsequent PDAP occurred in 420 (25.7%) participants during a median of 28 months of follow-up. Overall, LK duration in the first year was positively associated with a subsequent PDAP risk (per 3-month increments, adjusted HR, 1.13; 95%CI: 1.05–1.23). After categorization, patients with LK duration longer than 6 months had the highest adjusted HR of 1.53 (p = 0.005 vs. those without LK) for subsequent PDAP risk. A similar trend was also found for SLK duration. In a competing risk model, a similar trend was also observed. None of the variables, including demographic and PD characteristics, diabetes history, and several clinical measurements, significantly modified this association. The causative organisms of PDAP were similar to those previously reported. Conclusions: PD patients with longer LK duration in the first year had a higher subsequent PDAP risk

The Spermine Oxidase/Spermine Axis Coordinates ATG5‐Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis

Abstract Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF‐β1‐induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF‐β1‐induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence

Extracellular vesicle‐packaged ILK from mesothelial cells promotes fibroblast activation in peritoneal fibrosis

Abstract Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long‐term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell‐cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single‐cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD effluent. We demonstrated that transforming growth factor‐β1 (TGF‐β1) can substitute for PD fluid to stimulate mesothelial cells releasing EVs, which in turn promoted fibroblast activation and peritoneal fibrogenesis. Blockade of EVs secretion by GW4869 or Rab27a knockdown markedly suppressed PD‐induced fibroblast activation and peritoneal fibrosis. Mechanistically, injured mesothelial cells produced EVs containing high level of integrin‐linked kinase (ILK), which was delivered to fibroblast and activated them via p38 MAPK signalling pathway. Clinically, the expression of ILK was up‐regulated in fibrotic peritoneum of patients undergoing long‐term PD. The percentage of ILK positive EVs in PD effluent correlated with peritoneal dysfunction and the degree of peritoneal damage. Our study highlights that peritoneal EVs mediate communications between mesothelial cells and fibroblasts to initiate peritoneal fibrogenesis. Targeting EVs or ILK could provide a novel therapeutic strategy to combat peritoneal fibrosis

Current apparent treatment‐resistant hypertension in patients undergoing peritoneal dialysis: A multi‐center cross‐sectional study

Abstract Apparent treatment‐resistant hypertension (aTRH) is the most commonly used term to report resistant hypertension (RH) and is considered as a common problem in dialysis population. However, few reports have focused on peritoneal dialysis (PD) hypertensive patients. The authors conducted a multi‐center cross‐sectional study involving 1789 PD patients from nine centers in Guangdong, China. The prevalence of aTRH was estimated by home blood pressure (BP) monitoring. Evaluating drug adherence through Eight‐item Morisky Medication Adherence Scale (MMAS‐8) and pill counting was performed to assess RH in one PD center. Related factors of aTRH were analyzed using logistic regression analysis. The prevalence of aTRH in PD patients was estimated at 42.2% (755 out of 1789 hypertensive patients) based on home BP. Of those, 91.4% patients were classified as uncontrolled RH, 2.0% as controlled RH, and 6.6% as refractory hypertension. The prevalence of RH was 40.6% and 41.9% among those with medium/high adherence based on the MMAS‐8 scores and the pill counting rate, respectively. PD patients who were younger, with higher body mass index, with lower serum albumin and poorer dialysis adequacy were significantly associated with higher aTRH incident. In conclusion, the present study demonstrates a high prevalence of aTRH in PD population, which occurs in about two in five treated hypertensive patients. Nutritional status and dialysis adequacy might tightly associate with aTRH