The following represents additions to UpToDate since the last version that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.
GLOMERULAR DISEASE AND VASCULITIS
A classification of diabetic nephropathy was developed by the research committee of the Renal Pathology Society [1]. Four classes of glomerular lesions were described and lesions of interstitial fibrosis, tubular atrophy and vascular lesions were assigned scores based upon severity. A pilot study among five renal pathologists demonstrated good interobserver reproducibility. (See "Overview of diabetic nephropathy".)
A study of idiopathic membranous nephropathy reported outcomes of 328 patients with nephrotic range proteinuria (>3.5 g/day) secondary to biopsy-proven membranous nephropathy [2]. Among patients with protein excretion less than 8 grams/day, treatment with an ACE inhibitor or ARB increased the probability of complete or partial remission. A progressive reduction in protein excretion over one year of observation off immunosuppressive therapy predicted remission. (See "Treatment of idiopathic membranous nephropathy", section on Natural history and.) (See "Clinical trials of initial immunosuppressive therapy in idiopathic membranous nephropathy", section on 'Angiotensin inhibition'.)
Eleven cases of collapsing focal and segmental glomerulosclerosis associated with therapeutic doses of interferon-alpha, beta and gamma were identified from the archives of the Columbia Renal Pathology Laboratory [3]. Most patients presented with acute kidney injury and nephrotic syndrome, which reversed upon withdrawal of interferon. Additional benefits were not observed with immunosuppressive therapy. (See "Pathogenesis and diagnosis of focal segmental glomerulosclerosis", section on 'Treatment with interferon'.)
Among 68 patients with membranoproliferative glomerulonephritis (MPGN) who were negative for hepatitis B and C, 28 (41 percent) had serum or urine electrophoresis studies positive for a monoclonal gammopathy [4]. Of these,16 patients had monoclonal gammopathy of undetermined significance. (See "Classification and causes of membranoproliferative glomerulonephritis", section on 'Dysproteinemias'.)
HYPERTENSION
The Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD BP) randomly assigned 4733 patients with type 2 diabetes who were at high risk for cardiovascular events to either intensive therapy (goal systolic blood pressure less than 120 mmHg) or standard therapy (goal systolic blood pressure less than 140 mmHg) [5]. At a mean follow-up of 4.7 years, there was no difference in the rate of the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke or death from cardiovascular causes between the intensive versus standard therapy groups, nor in the all-cause mortality rate. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'ACCORD BP trial'.)
Guidelines for risk assessment, early recognition, and management of hypertension in patients treated with vascular endothelial growth factor (VEGF) signaling pathway inhibitors (eg, bevacizumab, sunitinib, sorafenib, pazopanib) are available [6]. (See "Overview of angiogenesis inhibitors", section on 'Hypertension'.)
ACUTE AND CHRONIC KIDNEY DISEASE
Significant improvement in hemodialysis catheter function was noted after intracatheter dwell with tenecteplase in a phase III placebo controlled study [7]. (See "Thrombosis associated with chronic hemodialysis vascular access: Catheters", section on 'Intraluminal lytic enzyme'.)
A retrospective study of 21 patients with pregnancy-associated hemolytic uremic syndrome (HUS) identified mutations of genes encoding complement-regulating proteins in 86 percent of cases [8]. Seventy-nine percent of patients presented during the postpartum period. (See "Acute kidney injury (acute renal failure) in pregnancy", section on 'Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome'.)
The CKD-EPI equation was developed to provide a more accurate estimate of glomerular filtration rate (GFR) among individuals with normal or only mildly reduced GFR. The CKD-EPI equation has now been shown in two separate studies to provide lower prevalence estimates of chronic kidney disease and more accurate risk prediction for adverse outcomes compared to the MDRD equation [9,10]. (See "Assessment of kidney function: Serum creatinine; BUN; and GFR", section on 'CKD-EPI equation'.)
FLUID AND ELECTROLYTES
The long-term administration of tolvaptan appears to be safe and effective among patients with chronic hyponatremia [11]. Responses were similar in heart failure and SIADH, and more modest in cirrhosis. (See "Hyponatremia in patients with heart failure" and "Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat", section on 'Vasopressin receptor antagonists'.)
TRANSPLANTATION
An increased incidence of angioedema has been noted in patients administered angiotensin-converting enzyme (ACE) inhibitors plus either sirolimus or everolimus [12]. (See "Sirolimus in renal transplantation", section on 'Others'.)
Encouraging allograft survival rates have been reported with kidney retransplantation after loss of the first allograft due to BK-induced nephropathy. A retrospective study of the OPTN database found that, among 126 such patients who received a retransplant, one and three year Kaplan-Meier allograft survival rates were 99 and 94 percent, respectively [13]. (See "Management of BK virus-induced (polyomavirus-induced) nephropathy in kidney transplantation", section on retransplantation.)
A retrospective analysis of the United States Renal Data System suggests that survival is improved after transplant nephrectomy among patients with a failed kidney allograft [14]. Although intriguing, further study is required to verify whether mortality improves with nephrectomy. (See "Withdrawal of immunosuppression after renal transplant failure", section on 'Indications for nephrectomy'.)
Improved survival with kidney transplantation compared with dialysis has been noted in a number of studies. It has now been reported with kidneys from donors after cardiac death. An observational cohort study from the Netherlands found that standard criteria kidney donation after cardiac death was associated with a 56 percent reduced risk for mortality compared with remaining on the transplant waitlist and continuing maintenance dialysis [15]. (See "Patient survival after renal transplantation", section on 'Survival compared with Dialysis'.)
GENETIC DISEASES
Activation of the mammalian target of rapamycin (mTOR) protein may contribute to cyst growth in autosomal dominant polycystic kidney disease (ADPKD). The inhibition of mTOR with rapamycin preserves renal function and inhibits epithelial cell proliferation and fibrosis in an orthologous mouse model of ADPKD in which the PKD-1 gene is conditionally deleted [16]. (See "Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth", section on 'Mammalian target of rapamycin (mTOR)',).
A proof-of-concept randomized crossover study evaluated the effect of rapamycin versus placebo on total kidney, parenchymal and cystic volumes among 21 patients with autosomal dominant polycystic kidney disease (ADPKD) [17]. At six months, cyst volume was stable on rapamycin and increased on conventional treatment whereas parenchymal volume increased on rapamycin and was unchanged on conventional treatment. (See "Course and treatment of autosomal dominant polycystic kidney disease", section on 'Mammalian target of rapamycin (mTOR)',).
A randomized trial examined the effect of a long-acting somatostatin (octreotide) versus placebo on liver and kidney cyst size in 34 patients with autosomal dominant polycystic kidney disease (ADPKD) and 8 with autosomal dominant polycystic liver disease [18]. At one year, the mean liver volume was decreased by almost five percent from baseline with octreotide but virtually unchanged with placebo; of 28 patients who received octreotide, 21 had a reduction in liver volume. Among patients with ADPKD, the mean kidney volume was stable on octreotide but increased on placebo. (See "Course and treatment of autosomal dominant polycystic kidney disease", section on 'Somatostatin'.)
PEDIATRIC NEPHROLOGY
Results from a trial that evaluated the effects of four parenteral fluid regimens in surgical pediatric patients suggest that isotonic saline at a maintenance fluid rate is less likely to result in hyponatremia and hypovolemia compared with other fluid regimens [19]. This study showed a two- to fourfold increase in mean antidiuretic hormone (ADH) concentrations during surgery and 24 hours postoperatively, which contributed to hyponatremia in 30 percent of children who received one-half normal saline (NS) fluid therapy and 10 percent of those who received NS eight hours after surgery. Fluid restriction (ie, 50 percent maintenance rate) resulted in hypovolemia in a significant number of patients regardless of fluid tonicity. These findings underscore the need for ongoing assessment of the patient's clinical condition and volume status when administering parental fluid therapy. (See "Maintenance fluid therapy in children", section on 'Hospitalized children'.)
A case report suggests that eculizumab, a monoclonal antibody that blocks complement activity by cleavage of C5, is effective in preventing relapse of atypical HUS after transplantation [20]. In this report, there has been no recurrence of disease or graft rejection in a child with atypical HUS and factor H mutation who has been treated with ongoing eculizumab therapy, which was started 10 days after renal transplantation. (See "Atypical hemolytic uremic syndrome in children", section on 'Complement dysregulation'.)
REFERENCES
- Tervaert, TW, Mooyaart, AL, Amann, K, et al. Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 2010; 21:556.
- Polanco, N, Gutierrez, E, Covarsi, A, et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol 2010; 21:697.
- Markowitz, GS, Nasr, SH, Stokes, MB, D'Agati, VD. Treatment with IFN-{alpha}, -{beta}, or -{gamma} is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2010; 5:607.
- Sethi, S, Zand, L, Leung, N, et al. Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy. Clin J Am Soc Nephrol 2010; 5:770.
- Cushman, WC, Evans, GW, Byington, RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362:1575.
- Maitland, ML, Bakris, GL, Black, HR, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst 2010; 102:596.
- Tumlin, J, Goldman, J, Spiegel, DM, et al. A phase III, randomized, double-blind, placebo-controlled study of tenecteplase for improvement of hemodialysis catheter function: TROPICS 3. Clin J Am Soc Nephrol 2010; 5:631.
- Fakhouri, F, Roumenina, L, Provot, F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010; 21:859.
- Matsushita, K, Selvin, E, Bash, LD, et al. Risk implications of the new CKD Epidemiology Collaboration (CKD-EPI) equation compared with the MDRD Study equation for estimated GFR: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis 2010; 55:648.
- White, SL, Polkinghorne, KR, Atkins, RC, Chadban, SJ. Comparison of the prevalence and mortality risk of CKD in Australia using the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study GFR estimating equations: the AusDiab (Australian Diabetes, Obesity and Lifestyle) Study. Am J Kidney Dis 2010; 55:660.
- Berl, T, Quittnat-Pelletier, F, Verbalis, JG, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol 2010; 21:705.
- Duerr, M, Glander, P, Diekmann, F, et al. Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients. Clin J Am Soc Nephrol 2010; 5:703.
- Dharnidharka, VR, Cherikh, WS, Neff, R, et al. Retransplantation after BK virus nephropathy in prior kidney transplant: an OPTN database analysis. Am J Transplant 2010; 10:1312.
- Ayus, JC, Achinger, SG, Lee, S, et al. Transplant nephrectomy improves survival following a failed renal allograft. J Am Soc Nephrol 2010; 21:374.
- Snoeijs, MG, Schaubel, DE, Hene, R, et al. Kidneys from donors after cardiac death provide survival benefit. J Am Soc Nephrol 2010; 21:1015.
- Shillingford, JM, Piontek, KB, Germino, GG, Weimbs, T. Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol 2010; 21:489.
- Perico, N, Antiga, L, Caroli, A, et al. Sirolimus Therapy to Halt the Progression of ADPKD. J Am Soc Nephrol 2010; 21:1031.
- Hogan, MC, Masyuk, TV, Page, LJ, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol 2010; 21:1052.
- Neville, KA, Sandeman, DJ, Rubinstein, A, et al. Prevention of hyponatremia during maintenance intravenous fluid administration: a prospective randomized study of fluid type versus fluid rate. J Pediatr 2010; 156:313.
- Zimmerhackl, LB, Hofer, J, Cortina, G, et al. Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome. N Engl J Med 2010; 362:1746.
