Buglioni, Alessia

Key Points Baseline kidney function and chronic structural injury strongly predicted both renal recovery and long-term clinical outcomes. Tubulointerstitial nephritis was the predominant lesion in Sjögren syndrome with renal involvement. Early detection and management of renal involvement in Sjögren syndrome are critical to preventing irreversible kidney damage. Background Renal involvement in primary Sjögren syndrome (SS) is uncommon but clinically consequential. Previous studies have been limited by small samples and incomplete biopsy data. We evaluated a large biopsy-confirmed cohort to characterize clinicopathologic features of SS with renal involvement and identify predictors of renal recovery and long-term outcomes. Methods We retrospectively identified adults with SS and kidney biopsy at Mayo Clinic (2012–2025). Clinical, laboratory, and histologic data were extracted. Predictors of complete renal recovery within 6 months, defined as serum creatinine (sCr) returning to within 25% of baseline or <1.4 mg/dl if baseline was unknown, were evaluated using logistic regression. Cox regression assessed long-term risk of a composite end point: newly developed or progressive CKD, ESKD, or all-cause mortality. Results Fifty-six patients were included (median age 57 years; 91% female). Extraglandular manifestations occurred in 76% and baseline CKD in 65%. The median sCr at baseline and biopsy was 1.3 and 1.6 mg/dl, respectively. Anti-Sjogren's syndrome antigen A, often linked with Ro ribonucleoprotein was positive in 80%. Low C3 occurred in 14% and low C4 in 25%. Tubulointerstitial nephritis was the predominant lesion (71%). Moderate/severe interstitial fibrosis/tubular atrophy and arteriosclerosis were present in 36% and 41%, respectively. Immunosuppressive therapy was applied in 84%. Complete recovery occurred in 67%. Over a median 3.9 years (interquartile range, 1.4–7.2), 43% reached the composite end point. Baseline sCr ≥2 mg/dl, 24-hour proteinuria ≥1 g, and presence of segmental glomerulosclerosis were associated with lower odds of recovery (odds ratio=0.16, 0.13 and 0.11, P = 0.02, 0.001 and 0.008, respectively) and higher long-term risk (hazard ratio=4.51, 2.92 and 3.52; P = 0.002, 0.01 and 0.02, respectively). Moderate/severe arteriosclerosis also increased long-term risk (hazard ratio=2.56; P = 0.03). Conclusions In biopsy-confirmed SS-related renal involvement, the severity of kidney dysfunction and the extent of chronic glomerular and vascular injury strongly predict renal prognosis. Early detection and targeted management of high-risk features may improve long-term renal outcomes.

Background: Vascular endothelial growth factor inhibitors (VEGF-I) are frequently used for cancer treatment. VEGF-I can cause proteinuria and acute kidney injury (AKI) with thrombotic microangiopathy (TMA) as a commonly described pathology, but other glomerular pathologies are not well characterized. We aim to describe the clinical characteristics and glomerular lesions associated with VEFG-I in a single center cohort. Methods: We performed a retrospective chart review of patients treated with VEGF-I and underwent kidney biopsies from 2010 to 2022 at the Mayo Clinic, Rochester, MN. Biopsy findings were reviewed by our pathologists. Data on patients’ characteristics, clinical course, and outcomes were abstracted. Descriptive statistics were used to report relevant patient characteristics and findings. Results: From 2010 to 2022, 19 kidney biopsies were performed for kidney dysfunction in patients on VEGF-I. Eleven had complete data, with a median age of 62 years (interquartile range 58–66 years); renal cell carcinoma (RCC) was the most common cancer (4 of 11 patients). TMA was noted in 8 of the 11 biopsies, with proteinuria as the most frequent indication for biopsy in these cases. Three patients had findings other than TMA. One developed anti-phospholipase A2 receptor negative membranous nephropathy; VEGF-I and pembrolizumab were discontinued, and prednisone improved proteinuria. Another patient had known cryoglobulinemia with nephrotic range proteinuria which was exacerbated by VEGF-I peaking at 11 g/day. Despite stopping VEGF-I and treating with prednisone and rituximab, kidney dysfunction progressed to end stage kidney disease (ESKD). A third patient had IgA nephropathy with concurrent diabetic changes, but proteinuria progressed even after stopping VEGF-I. Conclusion: In this case-series of patients treated with VEGF-I undergoing kidney biopsy, we describe the pathological characteristics, clinical course, and outcomes of patients with pathologies other than TMA. Our study adds information to the sparse literature on patients with renal dysfunction after receiving VEGF-I.

Key Points Our study found a high prevalence of monoclonal gammopathy (MG) in patients diagnosed with ANCA-negative pauci-immune crescentic GN. Patients with MG showed a higher degree of fibrosis on kidney biopsy than those without MG with higher mortality rate. Our data suggest an association between MG and ANCA-negative pauci-immune crescentic GN, emphasizing this population's need for MG testing and monitoring. Background In a small subset of patients with pauci-immune crescentic GN (PICGN), ANCA are not identified, and patients are referred to as having ANCA-negative vasculitis. The cause of the disease in this subset of patients has remained elusive. We explored the role of monoclonal gammopathy (MG) in those with ANCA-negative PICGN. Methods We conducted a retrospective study and identified patients with PICGN who had undergone ANCA and monoclonal testing. Those positive for ANCA were excluded. Results We identified 14 patients with ANCA-negative vasculitis, of whom eight (57%) tested positive for MG with a mean age of 60.3±12.2 years, 75% were female, and with a mean serum creatinine of 4.3±1.92 mg/dl. The most common monoclonal proteins were IgG ( n =4, 50%) and kappa ( n =4, 50%). One patient had diagnosis of multiple myeloma. Most common extra-renal manifestations were skin rash (leukocytoclastic vasculitis) and neuropathy. Kidney biopsy showed a higher degree of interstitial fibrosis and tubular atrophy compared with those without MG. The median follow-up time was 3.2 years, with 50% mortality in those with MG. Conclusions More than 50% of the patients with ANCA-negative PICGN have MG, and patients present with more evidence of fibrosis on kidney biopsy, with higher mortality rate observed in our cohort. Monoclonal proteins may trigger the development of PICGN; their specific role in the pathogenesis of this disease needs further investigation.

Key Points Preexisting CKD, elevated serum creatinine, and severe interstitial fibrosis and tubular atrophy were linked to poor renal prognosis in renal sarcoidosis. Steroid therapy was strongly associated with renal recovery and improved long-term outcomes in renal sarcoidosis. Early detection and management of renal involvement in sarcoidosis are critical to preventing irreversible kidney damage. Background Renal sarcoidosis (RS) is a rare but potentially severe manifestation of sarcoidosis, primarily affecting the kidneys through granulomatous interstitial nephritis and calcium metabolic disturbances. This study evaluates the clinicopathologic features and renal outcomes of biopsy-proven RS, focusing on identifying predictors of renal recovery and disease progression. Methods This retrospective study included 43 biopsy-proven RS at Mayo Clinic (2012–2024). Demographic, clinical, laboratory, and histopathologic data were analyzed. Renal recovery within 6 months was classified as complete, partial, or no recovery based on serum creatinine (sCr) changes. Long-term adverse composite outcomes included the CKD onset, CKD progression, ESKD, dialysis initiation, or death. Logistic regression and Cox proportional hazards regression were used to assess predictors of renal outcomes. Results Among the cohort, 84% exhibited interstitial nephritis, with granulomatous interstitial nephritis in 33%. Calcium phosphate deposits were found in 58% of cases. Hypercalciuria (90%) was more common than hypercalcemia (74%). Within 6 months, 86% achieved recovery (74% complete, 12% partial), while 40% experienced long-term adverse composite outcomes. Higher sCr at biopsy (≥2.4 mg/dl) and moderate-to-severe interstitial fibrosis and tubular atrophy were associated with reduced complete recovery and worse long-term outcomes, while preexisting CKD significantly increased the risk of adverse long-term outcomes. Steroid therapy significantly increased the likelihood of complete recovery and reduced the risk of adverse long-term outcomes. Conclusions Preexisting CKD, elevated sCr at biopsy, interstitial fibrosis and tubular atrophy, and steroid therapy are key predictors of renal outcomes in RS. Early diagnosis and intervention are crucial to preventing irreversible kidney damage.