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Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, which is characterized by edema, hypoalbuminemia, hyperlipidemia, lipiduria, and proteinuria. Determination of idiopathic membranous nephropathy (IMN) disease progression risk is important for guiding initial therapy, with immunosuppressive therapy being reserved for high-risk patients. Because IMN may spontaneously remit in approximately 30% of patients, it is important to carefully select which patients should begin immunosuppressive therapy so as to maximize clinical benefit while limiting toxicity. An observation period of at least 6 months with conservative management that includes the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers is recommended. Initial treatment in high-risk IMN is a 6-month course of alternating steroids and alkylating agents. Calcineurin inhibitors (CNIs) represent an alternative first-line therapeutic option for high-risk patients who refuse treatment with steroid or alkylating agent therapy or for whom these treatments are contraindicated. Additional options are essential for patients with IMN who fail to adequately respond to initial therapies or who cannot use recommended therapies due to contraindications or intolerance, risks associated with repetitive dosing with alkylating agents, or potential exacerbation of impaired renal function with CNIs. While evidence for the use of alternative therapies in IMN is modest at best, our review summarizes the available literature for rituximab, mycophenolate mofetil, adrenocorticotropic hormone, intravenous immunoglobulin, and azathioprine. Rituximab has generally demonstrated beneficial outcomes with limited toxicity. Evidence supports a role for mycophenolate mofetil, although the evidence is of low quality and limited duration. Results from ongoing studies are required before adrenocorticotropic hormone can be recommended as therapy for treatment-resistant patients. Intravenous immunoglobulin and azathioprine are unlikely to have a role in IMN. With the advent of new tools and biomarkers measuring disease activity combined with new data regarding possible treatment options, the management and prognosis of IMN are likely to improve.

Interleukin-1 (IL-1) inhibitors potentially have a role as antiinflammatory agents in refractory gout or for patients who are unable to tolerate conventional therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or glucocorticoids, for acute attacks. Additionally, IL-1 inhibitors may also help patients with polyarticular and tophaceous gout by making them less vulnerable to breakthrough attacks during initiation of chronic urate-lowering treatment, the mainstay of gout therapy. Because evidence highlights the role of proinflammatory cytokine IL-1 in the inflammation process during an acute gouty attack, IL-1 inhibitors are used to modulate the pathogenesis of a variety of autoinflammatory diseases, providing support for its potential role in the inflammatory process of gout. After NSAIDs, colchicine, and steroids, IL-1 inhibitors are beneficial as fourth-line therapy for acute gout attacks due to their high cost and limited clinical experience. The IL-1 inhibitors used in gout are anakinra, canakinumab, and rilonacept. Based on published evidence, anakinra has limited support in the form of anecdotal case reports to justify its use for treating gout. Canakinumab's toxic profile in clinical trials precludes its use in treating patients for gout, and rilonacept shows promise with a few well-designed studies to support its use in gout patients initiating urate-lowering treatment. When combined with current traditional therapies, these newer agents present clinicians and patients with more potential treatment options in the difficult-to-treat gout population.

Objective: There is substantial evidence for a renoprotective effect of inhibitors of the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). However, it is unclear whether dual RAS blockade has additional benefits when compared to monotherapy in this population and whether any benefits outweigh the risks. Data sources: A systematic review and meta-analysis of English language articles was performed using MEDLINE, EMBASE, CINAHL, and the Cochrane database of systematic reviews. Study selection: All randomized, controlled trials comparing RAS blockade to monotherapy in patients with overt proteinuria were included. Data extraction: Articles were reviewed independently by two of the authors using a standardized data collection form including study quality indicators. Data synthesis: All pooled analyses were based on random-effects models. The primary efficacy outcome measure was the percent reduction in proteinuria with combination therapy versus monotherapy measured by difference in means. Secondary outcomes included changes in systolic blood pressure (SBP), glomerular filtration rate (GFR), and serum potassium, and incidence of hyperkalemia. The primary safety outcome was hyperkalemia. Results: Compared to monotherapy, combination therapy with an angiotensin converting enzyme inhibitor (ACEI) plus angiotensin receptor blocker (ARB) reduced proteinuria by an additional 25% (mean difference -25, 95% CI -33,- 17), whereas combination therapy with an aldosterone antagonist (ALDOA) plus ACEI or ARB reduced proteinurea by an additional 32% (mean difference -32, 95% CI -37,-27). SBP after treatment with combination therapy vs. monotherapy was significantly lower with both the ACEI/ARB and ALDOA combinations. Dual therapy was associated with an increase in serum potassium, in particular with the ALDOA combination. Limitations: Most studies were small and of short duration, and none included major patient outcome data such as kidney failure or death. Conclusion: Dual RAS blockade in patients with DKD reduces proteinuria and SBP but increases the risk of hyperkalemia.