Paricalcitol and cinacalcet have disparate actions on parathyroid oxyphil cell content in patients with chronic kidney disease.

The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.

Green urine.

Urinalysis is an integral part of a thorough patient evaluation. Change in urine characteristics can give clues to help solve some of the diagnostic challenges faced by physicians. We discuss a case of a benign cause of green discoloration of urine caused by propofol infusion, which reversed following its discontinuation.

Granuloma annulare.

We present a case of a 77-year-old, diabetic male with a 20-year history of a migratory erythematous, asymptomatic, generalized, nonscaly, and nonitchy rash that started over the dorsum of his left hand. On examination, there were multiple annular erythematous plaques, distributed symmetrically and diffusely over his torso and arms, with central clearing and no scales. A punch biopsy of the skin helped us to arrive at the diagnosis of a generalized granuloma annulare (GA). GA is a benign, self-limiting skin condition of unknown etiology that is often asymptomatic. The cause of this condition is unknown, but it has been associated with diabetes mellitus, infections such as HIV, and malignancies such as lymphoma. These lesions typically start as a ring of flesh-colored papules that slowly progress with central clearing. Lack of symptoms, scaling, or associated vesicles helps to differentiate GA from other skin conditions such as tinea corporis, pityriasis rosea, psoriasis, or erythema annulare centrifugum. Treatment is often not needed as the majority of these lesions are self-resolving within 2 years. Treatment may be pursued for cosmetic reasons. Available options include high-dose steroid creams, PUVA, cryotherapy, or drugs such as niacinamide, infliximab, Dapsone, and topical calcineurin inhibitors.

Symptomatic hyperammonemia after lung transplantation: lessons learnt.

Hyperammonemia, post-orthotopic lung transplantation, is a rare but mostly fatal complication. Various therapies, including those to decrease ammonia generation, increase nitrogen excretion, and several dialytic methods for removing ammonia have been tried. We describe three lung transplant recipients who developed acute hyperammonemia early after transplantation. Two of the three patients survived after a multidisciplinary approach including discontinuation of drugs, which impair urea cycle, aggressive ammonia reduction with prolonged daily intermittent hemodialysis (HD), and overnight slow low-efficiency dialysis in conjunction with early weaning of steroids and other therapeutic measures. Our experience suggests that early initiation of dialysis, high dialysis dose, increased frequency, and HD preferably to less efficient modalities increases survival in these patients.

Anemia and chronic kidney disease: making sense of the recent trials.

Anemia is a very common complication of chronic kidney disease (CKD). Anemia confers significant risk of cardiovascular disease and contributes to decreased quality of life. Anemia in CKD patients can be multi-factorial, including but not invariably due to the underlying renal insufficiency. Identifying the type of anemia is important in this group of patients and can often be challenging. Diagnosing anemia of renal disease due to erythropoietin (EPO) deficiency is a diagnosis of exclusion. Erythropoiesis stimulating agents (ESA) are the mainstay for the treatment of anemia secondary to CKD. However, over the last four years the use of ESA in the treatment of anemia in CKD patients has undergone a severe interrogation as several trials have reported adverse outcomes with targeting higher hemoglobin (Hb) levels with these agents. Thereby, this review describes the pathophysiology of anemia in CKD patients, diagnosis and the current role of ESA's as it relates to anemia of CKD as well as safety and efficacy of ESA's.

Metabolic derangements seen in chronic kidney disease and end-stage renal disease patients.

The National Health and Nutrition Examination Survey (NHANES) shows increasing trends in the prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the US population. There is an inverse relationship between a declining glomerular filtration rate and mortality and morbidity. A wide spectrum of complex metabolic derangements contributes to a large extent for this increased mortality and morbidity. An overview of some of these metabolic derangements--like uremic dyslipidemia, uremic inflammation, and endocrine abnormalities affecting thyroid and sexual functioning of CKD patients--is provided. Understanding some of these metabolic derangements may help develop new and affective strategies to help reduce mortality and morbidity among CKD patients.

Role of Growth Hormone Deficiency and Treatment in Chronic Kidney Disease.

Malnutrition and inflammation are strong predictors of mortality in advanced kidney disease, especially in patients on renal replacement therapy. The complex relationship between kidney disease, uremia, and malnutrition significantly contributes to the increased morbidity and mortality in this patient population potentially through a relative deficiency in growth hormone (GH). With an approximate 26 million Americans currently affected by some stage of chronic kidney disease and a predicted 750,000 people to be on dialysis by 2020, there is a need to develop innovative strategies aimed at reducing the high mortality seen in dialysis patients. We will review evidence on one such intervention with infusion of recombinant GH to improve the nutritional and inflammatory state, thereby expecting to improve the mortality and morbidity in this patient population.

Stenting renal artery stenosis: what is the fuss all about?

Renal artery stenosis is the most common cause of secondary hypertension after exclusion of renal parenchymal disease and/or hypertensive nephrosclerosis. Atherosclerotic processes comprise the major contributors to this condition and account for 90% of the disease burden. Usually, the disease comes to light when there has been substantial morbidity resulting from several years of uncontrolled blood pressures and renal failure. Early recognition and intervention is warranted. Interventions include both medical and surgical modalities. Currently, there are several reliable diagnostic procedures to identify renal artery stenosis. However, once the disease process is identified, the management differs quite dramatically based on the patient population, the goals of therapy such as control of hypertension versus amelioration of ischemic nephropathy, availability of interventionists and so on. In this review, we discuss the importance of identifying atherosclerotic renal artery stenosis, the diagnostic modalities available and some of the interventions used to manage this disorder. We emphasize evidence based medicine and recent clinical trials such as the STAR trial.

Acquired factor VIII inhibitor in a nonhemophilia patient on hemodialysis: challenges in management.

It is well known that the uremic milieu predisposes patients to an increased risk of bleeding. We report a case of a patient on hemodialysis who developed recurrent unexplained bleeding episodes. His renal failure was secondary to systemic lupus erythematosus. Further investigations revealed that his bleeding was secondary to the development of acquired inhibitors to factor VIII: C following a flare up of his systemic lupus erythematosus. Management issues related to recurrent bleeding in this situation are discussed and reviewed.

Role of plasmapheresis in the management of myeloma kidney: a systematic review.

Multiple myeloma complicated by acute renal failure is a diagnosis often encountered by the practicing nephrologist. The role of plasmapheresis in such patients has been of interest for decades. Three randomized controlled trials (RCTs) and multiple observational trials have evaluated the potential role of plasmapheresis in the management of this condition. This systematic review presents the results of these trials regarding survival benefits, recovery from dialysis, and improvement in renal function. A comprehensive search revealed 56 articles. Of these, only 8 articles met our inclusion criteria (3 RCTs, 1 correction of results, and 4 observational trials). Two of the 3 RCTs showed no difference in survival benefit. Two of the 3 RCTs showed a greater percentage of patients stopping dialysis in the intervention group; however, these results were not reproduced in the largest trial. All the studies showed an improvement in renal function for patients receiving plasmapheresis; however, only 2 RCTs and 1 retrospective study showed a statistically significant improvement in renal function among patients who received plasmapheresis in comparison with a control group. Our systematic review does not suggest a benefit of plasmapheresis independent of chemotherapy for multiple myeloma patients with acute renal failure in terms of overall survival, recovery from dialysis, or improvement in renal function.