Lupus nephritis (LN) is an inflammatory condition of the kidneys that encompasses various patterns of renal disease including glomerular and tubulointerstitial pathology. It is a major predictor of poor prognosis in patients with systemic lupus erythematosus (SLE). Genetic factors, including several predisposing loci, and environmental factors, such as EBV and ultraviolet light, have been implicated in the pathogenesis. It carries a high morbidity and mortality if left untreated. Renal biopsy findings are utilized to guide treatment. Optimizing risk factors such as proteinuria and hypertension with renin-angiotensin receptor blockade is crucial. Immunosuppressive therapy is recommended for patients with focal or diffuse proliferative lupus nephritis (Class III or IV) disease, and certain patients with membranous LN (Class V) disease. Over the past decade, immunosuppressive therapies have significantly improved long-term outcomes, but the optimal therapy for LN remains to be elucidated. Cyclophosphamide-based regimens, given concomitantly with corticosteroids, have improved survival significantly. Even though many patients achieve remission, the risk of relapse remains considerably high. Other treatments include hydroxychloroquine, mycofenolate mofetil, and biologic therapies such as Belimumab, Rituximab, and Abatacept. In this paper, we provide a review of LN, including pathogenesis, classification, and clinical manifestations. We will focus, though, on discussion of the established as well as emerging therapies for patients with proliferative and membranous lupus nephritis.

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BackgroundDespite an inordinate share of health care resources being utilized by patients with kidney disease, morbidity and mortality in these patients remain high. Although renal biopsy is an intervention to identify potential treatment-modifiable causes of disease, large-scale data studying the safety and outcomes of percutaneous native kidney biopsy in hospitalized patients are lacking.MethodsWe queried the Nationwide Inpatient Sample database from 2008 to 2012 and identified all hospital admissions during which a percutaneous renal biopsy was performed. Patients <18 years of age or with a transplanted kidney were excluded. Data regarding associated renal pathology and procedure-related complications were collected and analyzed. Outcomes studied were length of stay, mortality and cost adjusted for inflation.ResultsA total of 118 064 hospital admissions were included in our analysis. The most common complications reported after percutaneous kidney biopsy were packed red blood cell transfusion (261/1000 cases), hematuria (129/1000 cases) and bleeding (78/1000 cases). Patients had an overall mortality of 1.8%. The mean length of stay for each hospitalization was 10.65 days, with a significant difference between elective and nonelective admissions (6.3 versus 11.7; P < 0.01). The average cost per hospitalization was US$22 917 after adjusting for inflation, again with a significant difference between elective and nonelective admissions (15 168 versus 24 780; P < 0.01).ConclusionOverall, percutaneous renal biopsy is considered a safe procedure; however, our study based on a national database demonstrates a relatively higher complication rate as compared with the limited prior available studies.

Insulin and hyperinsulinemia reduce renal fractional excretion of urate (FeU) and play a key role in the genesis of hyperuricemia and gout, via uncharacterized mechanisms. To explore this association further we studied the effects of genetic variation in insulin-associated pathways on serum urate (SU) levels and the physiological effects of insulin on urate transporters. We found that urate-associated variants in the human insulin (INS), insulin receptor (INSR), and insulin receptor substrate-1 (IRS1) loci associate with the expression of the insulin-like growth factor 2, IRS1, INSR, and ZNF358 genes; additionally, we found genetic interaction between SLC2A9 and the three loci, most evident in women. We also found that insulin stimulates the expression of GLUT9 and increases [14C]-urate uptake in human proximal tubular cells (PTC-05) and HEK293T cells, transport activity that was effectively abrogated by uricosurics or inhibitors of protein tyrosine kinase (PTK), PI3 kinase, MEK/ERK, or p38 MAPK. Heterologous expression of individual urate transporters in Xenopus oocytes revealed that the [14C]-urate transport activities of GLUT9a, GLUT9b, OAT10, OAT3, OAT1, NPT1 and ABCG2 are directly activated by insulin signaling, through PI3 kinase (PI3K)/Akt, MEK/ERK and/or p38 MAPK. Given that the high-capacity urate transporter GLUT9a is the exclusive basolateral exit pathway for reabsorbed urate from the renal proximal tubule into the blood, that insulin stimulates both GLUT9 expression and urate transport activity more than other urate transporters, and that SLC2A9 shows genetic interaction with urate-associated insulin-signaling loci, we postulate that the anti-uricosuric effect of insulin is primarily due to the enhanced expression and activation of GLUT9.