Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.

Background: FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 (APOL1) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors. Methods: CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤−5 ml/min per year), intermediate progressor (slope between 0 and −5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation. Results: Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36–81] versus low-risk participants 76 ml/min per 1.73 m² [interquartile range, 44–106]; P<0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P<0.001) in the high-risk versus low-risk groups. Conclusions: In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.

In patients with stage 4 or 5 chronic kidney disease or end-stage renal disease who received gadolinium-based contrast agents since 2010, diagnostic codes for potential nephrogenic systemic fibrosis or mimics were exceedingly rare.

Acute interstitial nephritis (AIN) is often induced by drugs and is a common cause of acute kidney injury. Clinically diagnosing AIN can often be challenging because these signs and symptoms rarely present in concert. The inflammatory pathology of AIN leads to renal tubule dysregulation, which can be clinically observed as glycosuria, eosinophilia, leukocytes or white blood cell casts, and proteinuria. We present a case of an otherwise healthy woman in her 30s with AIN presenting with acute kidney injury and glycosuria without pyuria. This patient had an atypical presentation of AIN that lacked classic diagnostic laboratory features and has been rarely reported. She had profound glycosuria in the setting of normoglycemia, which resolved following a course of corticosteroids. Glycosuria was most likely due to proximal tubule damage from AIN. This case supports previous hypotheses that drug-induced AIN can cause proximal tubule dysfunction resulting in glycosuria in the absence of other identifiable proximal tubule dysregulations. We hypothesize that resolution of AIN involves the repair and restoration of sodium-dependent glucose cotransporter function.