Podocyte density is reduced in kidney allografts with high‐risk APOL1 genotypes at transplantation

Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high‐risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high‐risk and low‐risk genotypes. Demographic characteristics were similar in high‐risk (n = 16) and low‐risk (n = 91) donors. Podocyte density was significantly lower in high‐risk than low‐risk donors (108 ± 26 vs 127 ± 40 podocytes/106um3, P = .03). Kaplan‐Meier graft survival (high‐risk 61% vs. low‐risk 91%, p‐value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9‐7.8) revealed higher graft loss in recipients of APOL1 high‐risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high‐risk APOL1 allografts (P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min2 in recipients of APOL1 high‐risk vs low‐risk kidney allografts, respectively. Kidneys from high‐risk APOL1 donors had worse outcomes versus low‐risk APOL1 genotypes. Lower podocyte density in kidneys from high‐risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors

Age of Onset and Disease Course in Biopsy-Proven Minimal Change Disease: An Analysis From the Cure Glomerulonephropathy Network.

RATIONALE & OBJECTIVE: Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response. STUDY DESIGN: Prospective, multicenter, observational study. STUDY PARTICIPANTS: CureGN participants with proven MCD on biopsy. EXPOSURE: Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period. OUTCOME: Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure. ANALYTICAL APPROACH: Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission. RESULTS: The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P LIMITATIONS: CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy. CONCLUSIONS: Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response. PLAIN-LANGUAGE SUMMARY: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab