Tuberous sclerosis complex and von Hippel-Lindau disease are distinct autosomal dominant tumor suppressor syndromes that can exhibit similar renal phenotypes and seem to share some signaling pathway components. Similarities exist in the current clinical management of, and the newly identified potential therapeutic approaches for, these conditions. This Review summarizes the pathophysiologic and therapeutic overlap between tuberous sclerosis complex and von Hippel-Lindau disease and highlights the results of recent drug trials in these settings.

Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a kappa-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking.

A 31-year-old woman with tuberous sclerosis complex presented with a 1 week history of subjective fever, chills, rigors, poor appetite and dizziness.

Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive medication in transplantation for over a decade. Owing to its efficacy and relatively benign adverse effect profile, its use has been investigated in the treatment of several glomerular diseases, as we describe in this Review. Of these, MMF has most extensively been studied in lupus nephritis. Randomized controlled trials have documented the value of MMF in both induction and maintenance therapy for severe lupus nephritis in several different geographic and ethnic populations, and have defined its potential toxicity. In minimal-change disease, focal segmental glomerulosclerosis and membranous nephropathy, promising but limited data on MMF treatment exist from small retrospective and prospective studies. Ongoing, larger, prospective trials, such as the NIH trial in focal segmental glomerulosclerosis, might clarify the value of MMF in the treatment of this disease. The efficacy of MMF in IgA nephropathy remains unclear, despite several small, controlled trials. Conflicting results might reflect differences in the disease process, differences in MMF metabolism, or varying responses to the immunosuppressive agent in different populations. Only through large, collaborative, controlled trials will the true role of MMF be defined for each glomerular disease.

This commentary discusses a study reported by Kumar et al. that compared outcomes of 56 patients with autosomal dominant polycystic kidney disease (ADPKD) started on peritoneal dialysis with those of a control group of nondiabetic patients matched for age, sex and year of starting peritoneal dialysis. During follow-up (mean 37 months), patient survival, technique survival and peritonitis rates were similar in the two groups. Peritoneal dialysis was not only possible but was also successful in 68% of patients. Although the study was well conducted and the results very encouraging, it did not address the relevant clinical issue of whether peritoneal dialysis is a less desirable option than hemodialysis in some patients with ADPKD, for example those with very large, cystic kidneys and/or a very large, cystic liver. Further studies to investigate renal replacement modalities in patients with ADPKD should relate study outcomes to the volumes of patients' kidneys and liver.

Cardiac troponin T (cTnT) levels are often elevated in chronic kidney disease and correlate with survival of patients receiving dialysis. This commentary discusses a recent paper by Hickson et al. that investigated whether a single cTnT measurement can predict survival of patients on the waiting list for renal transplantation. Elevated cTnT levels (>0.01 ng/ml) were associated with left ventricular hypertrophy, reduced left ventricular ejection fraction and ischemia or resting ventricular wall motion abnormalities on dobutamine stress echocardiography, and also predicted mortality independently of age, diabetes or history of heart disease. Although the authors recommend intensive cardiac evaluation in patients with high cTnT levels on transplantation waiting lists, predicting who is at highest risk of dying on the waiting list has no practical utility unless an intervention can reliably lower that risk. Until then, the time patients spend on dialysis should be minimized by rapid referral for transplantation, prompt and appropriate waitlisting and widespread encouragement of living donation.

Medical tourism is increasing owing to high costs of care, lack of availability or long waits for procedures, and improvements in technology and standards of care in many countries. Transplant tourism is one example of medical tourism that has been attracting increasing attention because of concerns over poor treatment and outcomes of both donors and recipients. Most such cases involve vended kidneys obtained from vulnerable populations, and both donors and recipients receive inferior care by US standards. This commentary discusses a paper by Gill et al. that compared outcomes of 33 transplant tourists with those of patients transplanted at a US center. Fewer complications and better outcomes were seen in patients transplanted in the US center than among transplant tourists. Large transplant centers with long waiting times are increasingly likely to see patients return newly transplanted from overseas; such patients require urgent attention, with particular consideration to infectious complications.

This article discusses the conclusions of a retrospective cohort study reported by Garg et al. on behalf of the Donor Nephrectomy Outcomes Research (DONOR) Network. This study compared the incidence of cardiovascular events in a cohort of kidney donors with that in a matched control population, to establish whether living kidney donation is associated with increased cardiovascular risk. Garg et al. found that living kidney donors had a very low risk of death or cardiovascular events that was not significantly different to that of the control population (2.0 vs 2.7 events per 1,000 person-years; hazard ratio 0.7, 95% CI 0.4-1.2). During follow-up, hypertension was diagnosed more frequently among donors than controls, but this finding might reflect the close monitoring of donors. Although the study provides reassuring information for counseling potential kidney donors, the sample of patients was not sufficiently large to resolve uncertainties over the influence of reduced kidney function on the risk of cardiovascular disease.

The rapid rise in the incidence and prevalence of obesity and the concomitant increase in the incidence and prevalence of hypertension have fueled investigation into the role of obesity in the pathogenesis of hypertension. The genetic background that predisposes obese individuals to hypertension is being elucidated, and the importance of adipose tissue as an endocrine organ in the pathogenesis of hypertension is increasingly being recognized. Visceral adipose tissue is critical in the production of pathologic cytokines that are thought to mediate obesity-induced hypertension. Changes in the types and levels of adipocytokines that result from the accumulation of aberrant adipose tissue directly leads to alterations in systemic vascular resistance, sodium retention and sympathetic nervous system activity. Key changes in adipocytokine levels seen in obesity-induced hypertension include increased leptin and adiponectin levels. Another important mechanism in obesity-induced hypertension is the generation of angiotensin II and direct stimulation of aldosterone production. The increased sympathetic nervous system activity seen in obesity-associated hypertension leads to increased renal sodium retention and increased systemic vascular resistance. Increased systemic vascular resistance can also occur directly in obese individuals through vascular fibrosis and lipid deposition. Obesity should no longer be simply considered as a marker of cardiovascular risk but should be regarded as an important and primary contributor to the pathophysiology of hypertension.