Management of Osteoporosis in CKD Khairallah, Pascale; Nickolas, Thomas L
Clinical journal of the American Society of Nephrology,
06/2018, Letnik:
13, Številka:
6
Journal Article
Recenzirano
Odprti dostop
CKD mineral and bone disease is a common complication of kidney disease, and it affects the majority of patients with moderate to severe CKD. Recently, prospective studies have shown that measurement ...of bone mineral density by dual energy x-ray absorptiometry predicts incident fracture, providing nephrologists the ability to risk classify patients for skeletal fragility and targeted antifracture strategies for the first time. Furthermore, an expanding body of literature and anecdotal evidence suggest that pharmacologic agents used to treat osteoporosis in the general population can be safely used in patients with CKD. This review highlights the effects of the Kidney Disease Improving Global Outcomes updates on the management of CKD-associated osteoporosis, discusses recent investigations on the effects of antiosteoporotic agents in patients with CKD, and provides an overview of novel antiosteoporosis agents and the potential challenges related to their use in CKD.
The novel coronavirus SARS-CoV-2 (coronavirus disease 19, or COVID-19) primarily causes pulmonary injury, but has been implicated to cause hepatic injury, both by serum markers and histologic ...evaluation. The histologic pattern of injury has not been completely described. Studies quantifying viral load in the liver are lacking. Here we report the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. A subset of liver tissue blocks were subjected to polymerase chain reaction (PCR) for viral ribonucleic acid (RNA). Peak levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated; median ALT peak 68 U/l (normal up to 46 U/l) and median AST peak 102 U/l (normal up to 37 U/l). Macrovesicular steatosis was the most common finding, involving 30 patients (75%). Mild lobular necroinflammation and portal inflammation were present in 20 cases each (50%). Vascular pathology, including sinusoidal microthrombi, was infrequent, seen in six cases (15%). PCR of liver tissue was positive in 11 of 20 patients tested (55%). In conclusion, we found patients dying of COVID-19 had biochemical evidence of hepatitis (of variable severity) and demonstrated histologic findings of macrovesicular steatosis and mild acute hepatitis (lobular necroinflammation) and mild portal inflammation. We also identified viral RNA in a sizeable subset of liver tissue samples.
Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The ...National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging.
This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman-Tukey double-arcsine transformations were used to stabilize variance as complications were rare.
A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location.
Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.
Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a ...circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS. Although immunogenetic factors play an important role in many glomerular diseases, their role in recurrent primary FSGS post-transplantation has not been systematically investigated. To address this, we retrospectively studied a multicenter cohort of 74 kidney allograft recipients with end stage kidney disease due to primary FSGS, confirmed by clinical and histologic parameters. After adjusting for race/ethnicity, there was a numeric higher frequency of HLA-A30 antigen in primary FSGS (19%) compared to each of 22,490 healthy controls (7%, adjusted OR=2.0, P=0.04) and 296 deceased kidney donors (10%, OR=2.1, P=0.03). Within the group of transplant patients with end stage kidney disease due to primary FSGS, donor HLA-A30 was associated with recurrent disease (OR=9.1, P=0.02). Multivariable time-to-event analyses revealed that recipients who self-identified as Black people had lower risk of recurrent disease, probably reflecting enrichment of these recipients with
high-risk genotypes. These findings suggest a role for recipient and donor immunogenetic makeup in recurrent primary FSGS post-transplantation. Further larger studies in well-defined cohorts of primary FSGS that include high-resolution HLA typing and genome-wide association are necessary to refine these hereditary signals.
Acid Load and Phosphorus Homeostasis in CKD Khairallah, Pascale, MD; Isakova, Tamara, MD, MMSc; Asplin, John, MD ...
American journal of kidney diseases,
10/2017, Letnik:
70, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ...ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. Study Design Cross-sectional. Setting & Participants 980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictors Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration < 22 mEq/L. Outcome & Measurements 24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. Results Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P < 0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P = 0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion ( P < 0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration ( P = 0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration <22 versus ≥22 mEq/L ( P < 0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n = 359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available. Limitations Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion. Conclusions In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.
Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients ...receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied.
We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with atrial fibrillation.
The study included 43,621 patients who were aged 18 years older when receiving a first kidney transplant between January 1, 2005, and September 30, 2012 and whose primary payer was Medicare (parts A and B) at the time of transplantation and the 6 months preceding it.
Dialysis modality used before transplant.
Time to incidence of atrial fibrillation up to 3 years posttransplant.
Multivariable Cox regression was used to estimate HRs.
Of 43,621 patients, 84.9% received hemodialysis and 15.1% received peritoneal dialysis before transplant. The mean ± SD age was 51 ± 13.6 years; 60.8% were male, 55.6% White, and 35.8% Black race. The mean dialysis vintage was 4.3 ± 2.8 years. Newly diagnosed atrial fibrillation after kidney transplant occurred in 286 patients (during 15,363 person-years) who had received peritoneal dialysis and in 2,315 patients (during 83,536 person-years) who had received hemodialysis. After multivariable adjustment, atrial fibrillation was 20% (95% CI, 4%-38%) more likely in those who had been receiving hemodialysis versus peritoneal dialysis, regardless of whether death was considered a competing risk or a censoring event. Each year of pretransplant dialysis vintage increased the risk of posttransplant atrial fibrillation by 6% (95% CI, 3%-9%).
Residual confounding; data from billing claims does not specify the duration of atrial fibrillation or whether it is valvular.
Pretransplant hemodialysis, as compared with peritoneal dialysis, was associated with higher risk of newly diagnosed atrial fibrillation after a first kidney transplant.
New-onset atrial fibrillation (AF) occurs in 7% of kidney transplant recipients in the first 3 years posttransplantation. We conducted this study to determine whether pretransplant dialysis modality was associated with posttransplant AF. We identified 43,621 patients; 84.9% used hemodialysis and 15.1% used peritoneal dialysis pretransplant. Multivariable Cox regression was used to estimate hazard ratios. We found that patients receiving hemodialysis pretransplant were at 20% increased risk of developing posttransplant AF as compared with patients receiving peritoneal dialysis. As our understanding of transplant-specific risk factors for AF increases, we may be able to better risk-stratify transplant patients and develop monitoring and management strategies that can improve outcomes.
AKI is common among hospitalized patients with coronavirus disease 2019 (COVID-19) and is an independent risk factor for mortality. Although there are numerous potential mechanisms underlying ...COVID-19-associated AKI, our current knowledge of kidney pathologic findings in COVID-19 is limited.
We examined the postmortem kidneys from 42 patients who died of COVID-19. We reviewed light microscopy findings in all autopsies and performed immunofluorescence, electron microscopy, and
hybridization studies for SARS-CoV-2 on a subset of samples.
The cohort had a median age of 71.5 years (range, 38-97 years); 69% were men, 57% were Hispanic, and 73% had a history of hypertension. Among patients with available data, AKI developed in 31 of 33 patients (94%), including 6 with AKI stage 1, 9 with stage 2, and 16 with stage 3. The predominant finding correlating with AKI was acute tubular injury. However, the degree of acute tubular injury was often less severe than predicted for the degree of AKI, suggesting a role for hemodynamic factors, such as aggressive fluid management. Background changes of hypertensive arterionephrosclerosis and diabetic glomerulosclerosis were frequent but typically mild. We identified focal kidney fibrin thrombi in 6 of 42 (14%) autopsies. A single Black patient had collapsing FSGS. Immunofluorescence and electron microscopy were largely unrevealing, and
hybridization for SARS-CoV-2 showed no definitive positivity.
Among a cohort of 42 patients dying with COVID-19, autopsy histologic evaluation revealed acute tubular injury, which was typically mild relative to the degree of creatinine elevation. These findings suggest potential for reversibility upon resolution of SARS-CoV-2 infection.
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