Lynn E. Schlanger

Cholecalciferol (Vitamin D3) Therapy and Vitamin D Insufficiency in Patients with Chronic Kidney Disease: A Randomized Controlled Pilot Study

OBJECTIVE To investigate the efficacy of cholecalciferol (vitamin D3) in raising serum 25-hydroxyvitamin D (25[OH)]D) levels and reducing parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD). METHODS In this double-blind, randomized controlled pilot study, participants with CKD stage 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2), vitamin D insufficiency (serum 25[OH]D <30 ng/mL), and serum intact PTH levels >70 pg/mL were randomly assigned to receive either 50 000 IU of cholecalciferol or placebo once weekly for 12 weeks. Primary outcomes (25[OH]D and PTH levels) were measured at baseline, week 6, and week 12. Secondary outcomes (1,25-dihydroxvitamin D and bone turnover markers) were measured at baseline and week 12. Because of skewed data distribution, statistical analyses were performed on a logarithmic scale. The difference between the group means was exponentiated to provide the geometric mean ratio. A linear mixed model using an unstructured variance-covariance matrix was used to examine change in the primary and secondary outcomes over time. RESULTS Geometric mean serum 25(OH)D concentrations of the study groups were similar at baseline (P = .77). At week 6, a significant difference between the treatment and placebo groups was detected (P = .001); this difference was maintained at week 12 (P = .002). Among cholecalciferol-treated participants, serum 25(OH)D concentration increased on average from 17.3 ng/mL (95% confidence interval [CI], 11.8-25.2) at baseline to 49.4 ng/mL (95% CI, 33.9-72.0) at week 12. As-treated analysis indicated a trend toward lower PTH levels among cholecalciferol-treated participants (P = .07). CONCLUSION Weekly cholecalciferol supplementation appears to be an effective treatment to correct vitamin D status in patients with CKD.

Electrolytes in the Aging

The elderly population in the United States continues to grow and is expected to double by 2050. With aging, there are degenerative changes in many organs and the kidney is no exception. After 40 years of age, there is an increase in cortical glomerulosclerosis and a decline in both glomerular filtration rate and renal plasma flow. These changes may be associated with an inability to excrete a concentrated or a dilute urine, ammonium, sodium, or potassium. Hypernatremia and hyponatremia are the most common electrolyte abnormalities found in the elderly and both are associated with a high mortality. Under normal conditions, the elderly are able to maintain water and electrolyte balance, but this may be jeopardized by an illness, a decline in cognitive ability, and with certain medications. Therefore, it is important to be aware of the potential electrolyte abnormalities in the elderly that can arise under these various conditions to prevent adverse outcomes.

Incorporating Geriatric Assessment into a Nephrology Clinic: Preliminary Data from Two Models of Care

Older adults with advanced chronic kidney disease (CKD) experience functional impairment that can complicate CKD management. Failure to recognize functional impairment may put these individuals at risk of further functional decline, nursing home placement, and missed opportunities for timely goals‐of‐care conversations. Routine geriatric assessment could be a useful tool for identifying older adults with CKD who are at risk of functional decline and provide contextual information to guide clinical decision‐making. Two innovative programs were implemented in the Veterans Health Administration that incorporate geriatric assessment into a nephrology visit. In one program, a geriatrician embedded in a nephrology clinic used standardized geriatric assessment tools with individuals with CKD aged 70 and older (Comprehensive Geriatric Assessment for CKD) (CGA‐4‐CKD). In the second program, a nephrology clinic used comprehensive appointments for individuals aged 75 and older to conduct geriatric assessments and CKD care (Renal Silver). Data on 68 veterans who had geriatric assessments through these programs between November 2013 and May 2015 are reported. In CGA‐4‐CKD, difficulty with one or more activities of daily living (ADLs), history of falls, and cognitive impairment were each found in 27.3% of participants. ADL difficulty was found in 65.7%, falls in 28.6%, and cognitive impairment in 51.6% of participants in Renal Silver. Geriatric assessment guided care processes in 45.4% (n = 15) of veterans in the CGA‐4‐CKD program and 37.1% (n = 13) of those in Renal Silver. Findings suggest there is a significant burden of functional impairment in older adults with CKD. Knowledge of this impairment is applicable to CKD management.

Granulomatous Interstitial Nephritis and Uveitis Presenting as Salt-Losing Nephropathy

Salt-wasting nephropathy is a rare syndrome in which renal insufficiency is associated with extracellular volume depletion from marked natriuresis in the absence of adrenal insufficiency or diuretics. We report the clinical course of a 23-year-old woman with renal insufficiency, in association with orthostatic hypotension and salt wasting. A combination of daily infusion of saline, a high-salt diet and oral fludrocortisone did not compensate for her salt loses. Renal biopsy showed noncaseating granulomas and marked interstitial inflammation. Renal function and salt loss improved with prednisone therapy and 6 months after withdrawal of steroids, her renal function remains stable.

Proliferative C4 Dense Deposit Disease, Acute Thrombotic Microangiopathy, a Monoclonal Gammopathy, and Acute Kidney Failure

Dense deposit disease (DDD) is a rare form of glomerulonephritis that has recently been reclassified under the broad group of C3 glomerulopathy, which also includes C3 glomerulonephritis. C3 glomerulopathy is characterized by predominant C3 staining on immunofluorescence microscopy and dysregulation of the alternative complement pathway. We present a case of DDD concurrent with acute thrombotic microangiopathy (TMA) in a 54-year-old white man. The patient presented with acute kidney injury, and a kidney biopsy showed segmental highly electron-dense intramembranous deposits and large rounded mesangial electron-dense deposits consistent with DDD and coexisting glomerular and vascular thrombosis consistent with concurrent acute TMA. However, immunofluorescence microscopy did not show C3 staining in nonsclerotic glomeruli, excluding C3 DDD. Rather, there was dense staining for C4d along the glomerular capillaries, suggesting C4 DDD. Activity of the alternative complement pathway was normal. To our knowledge, this is the first reported case of C4 DDD concurrent with TMA. One previous case report of C4 DDD had been reported, though in a teenage girl. These 2 cases suggest that C4 DDD is a rare entity and should be distinguished from the C3 glomerulopathies.

Geriatric Nephrology: Old or New Subspecialty

In the 1980s geriatric nephrology was introduced as a subspecialty in anticipation of the increased number of elderly and very elderly people during the 21st century. There has been more clinical research dedicated to geriatric nephrology, education on the subspecialty has been implemented at national and university level, and funds for career development have been instituted over the past two decades. Our treatment of the elderly and very elderly patients seems to be more focused on their biologic age rather than chronologic age; they undergo diagnostic tests such as kidney biopsies and are candidates for kidney transplant. Although great strides have been made in the assimilation of geriatrics into nephrology more has to be done. This article examines the areas of research that encompass geriatric nephrology and clinic observations applicable to the care of the geriatric population.

Reversible Renal Failure in an Elderly Woman With Renal Artery Stenosis

Renal artery stenosis not only causes severe hypertension, but if left untreated, can progress to renal failure. A 64-year-old woman with a serum creatinine of 1.8 mg/dL and mild proteinuria developed progressively severe hypertension that was resistant to a calcium channel blocker. The patient received lisinopril, which was discontinued after 2 days because of nonspecific symptoms. One week later, an intravenous pyelogram showed a normal-sized but poorly functioning left kidney and a nonfunctional right kidney. The serum creatinine increased to 11.7 mg/dL and the patient was begun on hemodialysis. A renal arteriogram performed 6 weeks later for persistent hypertension showed bilateral renal artery occlusion; renal vein renin values from the left kidney were higher than those from the right kidney. After 11 weeks of hemodialysis, thrombolytic therapy followed by angioplasty was performed. Three weeks later, the renal function had returned to baseline (serum creatinine of 1.8 mg/dL) and hypertension was controlled with a beta-blocker. Renal artery stenosis is a potentially reversible cause of renal failure and should be considered in the evaluation of elderly patients with hypertension, even in the presence of renal failure.

Aging and the Kidney: Clinical and Pathophysiological Issues

The aging kidney undergoes structural and functional phenotypic changes with time. There is a decline in GFR, renal plasma flow (RPF), and tubular function, characterized histologically by glomerulosclerosis, tubulointerstitial fibrosis and atrophy. These changes appear to be influenced by the environment, genetic factors and gender, and result in a pro-fibrotic, pro-inflammatory, apoptotic state. These adaptations may increase the elderly’s susceptibility to acute and chronic kidney disease, allograft failure and be responsible for the higher mortality rates frequently seen in the elderly. Modification of the cellular and molecular mechanisms underlying age-associated renal changes, with various medications, transcription factor inhibitors or caloric restriction, may modify or attenuate these changes and prevent progression to CKD.

Mineral and Bone Disorders in Chronic Kidney Disease

A 64-year-old woman with a history of chronic kidney disease (CKD) Stage 4 [estimated glomerular filtration rate (eGFR) of 17 cc/min/1.73 mm2] is referred for evaluation of “poor kidney function.” Over the last month she has complained of itching, skin eruptions on her arms and back, and nonspecific bone pain. She has been unable to sleep at night and denies changes in soap, laundry detergent, or perfume. She has never been prescribed a phosphate binder or vitamin D, has no dietary restrictions, and dines out a few times per week. She usually consumes bacon and eggs for breakfast, a sandwich with cheese and cold cuts for lunch, and beans and chicken or fish for dinner. She has never been to see a nutritionist but feels her dietary intake is adequate. Physical exam is remarkable for diffuse areas of excoriation on her arms and back with raised hard central pustules. Pertinent laboratory values: phosphorous—7.5 mg/dL, calcium—7.9 g/dL, albumin—4 g/dL, creatinine—3.5 mg/dL, urea—50 mg/dL, alkaline phosphatase—180 mg/dL, bicarbonate—20 mEq/L. Intact PTH and vitamin D 25 are pending at the end of her visit.

Vasopressin in the Kidney: Historical Aspects

Abstract In the past century, scientific research has made great strides and has unraveled the pathophysiology for water homeostasis and its dysregulation in certain disease processes such as nephrogenic diabetes insipidus and hyponatremia. In the mid-20th century, experimental infusion of a pituitary gland extract was noted to cause antidiuresis and concentrated urine leading to the discovery of the antidiuretic hormone, ADH. The ADH was found to be produced in the hypothalamus neurons and stored and secreted by the pituitary gland and resulting in a downstream effect on the “shuttling” of water channels to luminal surface in the toad bladder and in the collecting duct. In the latter half of the 20th century with advancements in molecular biology and immunohistochemistry, vasopressin receptors, urea transporters, and aquaporins (water channels) were identified as well as their various roles in water homeostasis. The V2 (vasopressin) receptor was isolated in the distal nephron tubules and determined to be responsible for water balance while V1a and V1b receptors were not. Similarly, two of the six isoforms of urea transporters, UT-A1 and UT-A3, were localized in the inner medullary collecting ducts; both of these are stimulated by vasopressin and have an important role in maintenance of the countercurrent system. Of the 13 aquaporins identified, 3 were localized in the collecting ducts; aquaporin 2, 3, and 4, with only aquaporin 2 regulated by vasopressin and “shuttled” to luminal membrane. These various discoveries, translating from bench research to clinical studies, have given us the opportunity to treat various disease states such as chronic hyponatremia, adult polycystic kidney disease, central diabetes insipidus, and genetic and acquired nephrogenic diabetes insipidus.