Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury.

Background: Hyperoxaluria is a major cause of oxalate nephropathy, which can lead to impaired renal function presenting as acute kidney injury, acute on chronic kidney disease, or chronic kidney disease. The Chronic Renal Insufficiency Cohort study showed that higher urinary oxalate is associated with renal outcome in patients with chronic kidney disease, supporting the nephrotoxicity of oxalate. Therefore, a better understanding of the role of oxalate in kidney injury is needed. This review describes the metabolism of oxalate and the clinical and pathology presentation of oxalate nephropathy. It also summarizes the available evidence for the underlying pathogenic mechanism and the development of treatments for oxalate-induced kidney injury. Summary: Disruption to any key step in the oxalate pathway including abnormal endogenous generation, ingestion of abnormally high dose of oxalate, increased absorption or attenuation of oxalate degradation in the gut, and reduced excretion through the kidney may lead to disrupted oxalate homeostasis. Oxalate nephropathy is mainly caused by hyperoxaluria. Oxalate crystal deposition in the kidney is usually accompanied with tubular toxicity, obstruction, interstitial fibrosis, and tubular atrophy. The mechanism of oxalate-induced renal injury has not been fully clarified. Evidence from both in vivo and in vitro studies shows that NLRP3 inflammasome activation and macrophage infiltration are involved in the processes of crystal adhesion, aggregation, and elimination and promote intrarenal inflammation and renal fibrosis. Novel treatment strategies have been developed and targeted therapies tested for oxalate nephropathy. Key Messages: Prompt diagnosis and management may help to reduce the deposition of calcium oxalate crystals in the kidney. Further studies are needed to clarify the underlying mechanisms to help develop more targeted therapies for oxalate nephropathy.

Determinants on urinary excretion of oxalate and other key factors related to urolithiasis among patients with chronic kidney disease: a single center study.

PURPOSE: Urolithiasis is a known risk factor for chronic kidney disease (CKD). However, how CKD might affect the risk of incidence of urolithiasis is not widely studied. METHODS: Urinary excretion of oxalate as well as other key factors related to urolithiasis was analyzed in a single center study of 572 patients with biopsy-proven kidney disease. RESULTS: The mean age of the cohort was 44.9 years and 60% were males. The mean eGFR was 65.9 ml/min/1.73 m2. Median urinary excretion of oxalate was 14.7 (10.4-19.1) mg/24-h and associated with current urolithiasis (OR 12.744, 95% CI: 1.564-103.873 per one logarithm transformed unit of urinary oxalate excretion). Oxalate excretion was not associated with eGFR and urinary protein excretion. Oxalate excretion was higher in patients with ischemia nephropathy as compared with patients with glomerular nephropathy and tubulointerstitial nephropathy (16.4 vs 14.8 vs 12.0 mg, p = 0.018). And ischemia nephropathy (p = 0.027) was associated with urinary oxalate excretion on adjusted linear regression analysis. Urinary excretion of calcium and uric acid was correlated with eGFR and urinary protein excretion (all p < 0.001), with ischemia nephropathy and tubulointerstitial nephropathy associated with uric acid excretion (both p < 0.01) as well. Citrate excretion was correlated with eGFR (p < 0.001) on adjusted linear regression. CONCLUSION: Excretion of oxalate and other key factors related to urolithiasis was differentially associated with eGFR, urinary protein, and pathological changes in CKD patients. The influence of these intrinsic traits of the underlining kidney disease should be considered when evaluating urolithiasis risk in patients with CKD.

Prevalence and clinical association of hyperechoic crystal deposits on ultrasonography in patients with chronic kidney disease: a cross-sectional study from a single center.

BACKGROUND: Hyperechoic crystal deposits can be detected in the kidney medulla of patients with gout by ultrasonography examination. Chronic kidney disease (CKD) is usually accompanied with hyperuricemia. Whether hyperechoic crystal deposition could be detected by ultrasonography in CKD patients, and its clinical association are unknown. METHODS: Five hundred and fifteen consecutive CKD patients were included in this observational study. Clinical, biochemical and pathological data were collected and analyzed. RESULTS: Altogether, 234 (45.4%) patients were found to have hyperuricemia and 25 patients (4.9%) had gout history. Hyperechoic crystal deposits in kidney medulla were found in forty-four (8.5%) patients, on ultrasonography. Compared with patients without hyperechoic crystal deposits, patients with deposits were more likely to be male, younger, with gout history and presenting with higher serum uric acid level, lower estimated glomerular filtration rate, lower urine pH, lower 24 h-urinary citrate and uric acid excretion, and with a higher percentage of ischemic nephropathy (all p < 0.05). On multivariable logistic analysis, the hyperechoic depositions were associated with age [0.969 (0.944, 0.994), p = 0.016], serum uric acid level [1.246 (1.027, 1.511), p = 0.026], Sqrt-transformed 24 h-urine uric acid excretion [0.923 (0.856, 0.996), p = 0.039], and ischemic nephropathy [4.524 (1.437, 14.239), p = 0.01], respectively. CONCLUSIONS: Hyperechoic crystal deposition can be detected in kidney medulla by ultrasonography; in CKD patients their presence was associated with hyperuricemia as well as with ischemic nephropathy.

Acute oxalate nephropathy: A potential cause of acute kidney injury in diabetes mellitus-A case series from a single center.

Background: Acute oxalate nephropathy (AON) is an uncommon condition that causes acute kidney injury (AKI), characterized by the massive deposition of calcium oxalate crystals in the renal parenchyma. In previous studies, urinary oxalate excretion has been found to be increased in patients with diabetes mellitus (DM). Here, we report a case series of diabetic patients with AKI with biopsy-proven AON, aiming to alert physicians to the potential of AON as a trigger of AKI in diabetic patients in clinical practice. Materials and methods: Cases with pathological diagnosis of AON who presented with AKI clinically and had DM between January 2016 and December 2020 were retrospectively enrolled. Their clinical and pathological manifestations, treatment, and prognosis were collected. Results: Six male patients with biopsy-proven AON out of a total of 5,883 native kidney biopsies were identified, aged 58.3 ± 9.1 years at the time of kidney biopsy. Only one patient who had received Roux-en-Y gastric bypass surgery took oxalate-rich food before the onset of the disease. None of them had clinical features of enteric malabsorption. Three patients were currently on renin-angiotensin system inhibitor treatment for hypertension, and 5 of them received non-steroidal anti-inflammatory drugs. Three patients presented with oliguria and 4 patients needed dialysis at the beginning with none requiring dialysis at discharge. Four patients received a course of corticosteroid treatment empirically. Among them, two patients had estimated glomerular filtration rate (eGFR) recovered to over 60 ml/min/1.73 m2, while the other two patients remained with kidney dysfunction at the last follow-up. In two patients without corticosteroid treatment, one patient fully recovered with eGFR over 90 ml/min/1.73 m2 and the other patient remained with kidney dysfunction at the last follow-up. Conclusion: AON might be a rare but potentially trigger of AKI in patients with DM. A kidney biopsy could help physicians to make the correct diagnosis. The proper treatment to alleviate oxalate-induced injury needs to be further studied.

Case Report: A Rare Case of Lupus Nephritis Associated With Mantle Cell Lymphoma.

In this research, we described a very rare case of secondary lupus nephritis associated with B-cell lymphoma. An 84-year-old man was hospitalized at our institute for lower extremity edema persisting for over 2 months. He was diagnosed with systemic lupus erythematosus based on clinical and laboratory criteria, which showed impaired renal function and nephrotic syndrome with predominant hematuria. Renal biopsy showed IV+V lupus nephritis with highly infiltrated lymphoid cells in the kidney. Secondary lupus nephritis was suspected based on the possible pathogenesis of glomerular injury due to mantle cell lymphoma. Low-dose dexamethasone, rituximab, and lenalidomide were immediately started on the patient, and his renal function was improved after the first cycle of chemotherapy.