Direct evidence of podocyte damage in cardiorenal syndrome type 2: preliminary evidence.

BACKGROUND: Renal structural alterations have been partially uncovered in cardiorenal syndrome (CRS). Patients with CRS may have evidence of tubular damage, but markers of glomerular damage other than proteinuria have not been thoroughly investigated. The nature of renal damage in CRS may have therapeutic implications, as glomerular damage requires tight blood pressure control and renin-angiotensin-aldosterone system (RAAS) inhibition. The present investigation evaluates patients with CRS type 2 (CRS-2) for direct evidence of glomerular damage as evidenced by the presence of urinary podocin. METHODS: The presence of glomerular damage was assessed in acutely decompensated patients with CRS-2 and healthy controls. Urinary podocin was determined by quantification of a tryptic peptide of podocin with high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Morning urine samples were collected for podocin, creatinine (Cr), and protein. Urinary podocin was expressed in femtomoles of podocin/milligram of Cr. RESULTS: The urinary podocin/Cr ratio was greater in patients than in controls (0.37 ± 0.77 vs. 0.06 ± 0.05 fmol podocin/mg Cr, p = 0.04). A total of 40% of the patients had a urinary podocin/Cr ratio greater than the upper limit of normal (>0.2 fmol podocin/mg Cr). Patients with an elevated podocin/Cr ratio were more likely to have received ≤50% of the maximum dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.04) than patients with a podocin/Cr ratio in the normal range. CONCLUSIONS: CRS-2 may be associated with glomerular damage as evidenced by an elevated urinary podocin/Cr ratio. Modulators of RAAS may have a protective effect on urinary podocin loss.

Quantification of asymptomatic kidney stone burden by computed tomography for predicting future symptomatic stone events.

OBJECTIVE: To find the optimal characterization of asymptomatic radiographic stone burden on computed tomography (CT) scans. METHODS: A survey was sent to stone formers who underwent a CT scan while asymptomatic during a stone clinic evaluation. Symptomatic stone passage events after CT scan were detected by survey and medical record review. Radiographic stone burden was quantified by number of stones, largest stone diameter, automated total stone volume (TSV), and bilateral stones and then compared as predictors of stone events. RESULTS: There were 550 stone formers; 43% had a stone event for a median of 4.7 years after the CT scan. Stone burden by quartiles was 0-1, 2-3, 4-6, and ≥7 for number of stones; 0-2, 3-4, 5-7, and ≥8 mm for largest stone diameter; and 0-8, 9-78, 79-280, and ≥281 mm(3) for TSV; 48% had bilateral stones. The hazard ratios (HRs) for symptomatic event was 1.30 (P <.001) for the number of stones per quartile, 1.26 (P <.001) for largest stone diameter per quartile, 1.38 (P <.001) for TSV per quartile, and 1.80 (P <.001) for bilateral stones. On multivariate analysis, only TSV was an independent predictor of symptomatic events (HR, 1.35 per quartile; P = .01). This risk of events with TSV was also independent of demographics, urine chemistries, and stone composition. Among the 53 patients with interim events between CT scans, a rapid increase in TSV between CT scans (>570 mm(3) per year) predicted subsequent events (HR, 2.8; P = .05). CONCLUSION: Automated TSV is more predictive of symptomatic events than manual methods for quantifying stone burden on CT scan.

Seronegative anti-GBM Disease with Coexistent ANCA Positivity.

Anti-glomerular basement membrane disease has been reported to coexist with anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis. Seronegative anti-GBM disease has been previously described and mostly blamed for the relative insensitivity of earlier serologic assays. A 58-year-old male was transferred to our facility for acute kidney injury. Prior to his hospital admission, the patient had a 2 week history of progressive fatigue, fevers, anorexia, vomiting, decreased urine output, sinus congestion, and non-productive cough. His creatinine reached 13 mg/dL. P-ANCA was positive, anti GBM antibody was negative twice, and urinalysis showed hematuria. Chest x-ray demonstrated diffuse opacities, concerning for pulmonary hemorrhage. Renal biopsy showed a severe necrotizing and crescentic glomerulonephritis with circumferential crescents. There was bright linear glomerular basement membrane staining with IgG consistent with anti-GBM disease. Given these findings, the patient was started on oral cyclophosphamide (160 mg daily), in addition to pulse dose methylprednisolone. He was also initiated on therapeutic plasma exchange. Due to worsening renal function, hemodialysis was started. The patient was discharged from the hospital and completed a course of treatment with cyclophosphamide and prednisone but remains oligo-anuric and hemodialysis dependent at 150 days since presentation. This case highlights the importance of tissue diagnosis in situations similar to this.