Incidence of Hyponatremia with High-Dose Trimethoprim-Sulfamethoxazole Exposure.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used at high doses for treatment of pneumocystis pneumonia and other infections. Trimethoprim is structurally related to the potassium-sparing diuretic amiloride and has been associated with hyperkalemia and hyponatremia through blocking of epithelial sodium channels in the distal nephron. The incidence of hyponatremia in hospitalized patients treated with high-dose TMP-SMX is unknown. METHODS: We performed a single-center retrospective chart review of all hospitalized patients who received high-dose TMP-SMX (n = 235) from January 2012 to July 2014. Patients with congestive heart failure, cirrhosis, estimated glomerular filtration rate <30 mL/min/1.73 m2, baseline hyponatremia, and those on other medications associated with hyponatremia were excluded. Hyponatremia was defined as a serum sodium level <136 mEq/L. RESULTS: Analysis was restricted to 76 unique patients who received more than 8 mg/kg/d of TMP for ≥3 days. Mean starting serum sodium at time of TMP-SMX initiation was 138.4 ± 2.1 mEq/L. Fifty-five patients (72.3%) developed hyponatremia while on therapy, of which 43.6% (n = 24) were cases of serum sodium <130 mEq/L. Mean sodium at the time of nadir was 131.6 ± 5.1 mEq/L. Hyponatremia was noted, on average, 5.5 days after initiation of therapy, with more severe hyponatremia development among African American patients. Urine sodium concentrations were available for 40.0% (22/55) of incident hyponatremia cases, with mean urinary sodium of 104.8 ± 55.9 mEq/L. Hyponatremia often resolved within 3 weeks of drug discontinuation. CONCLUSIONS: There is a high incidence (72.3%) of hyponatremia associated with the use of high-dose TMP-SMX among hospitalized patients. This is an overlooked and potentially reversible cause of hyponatremia.

Bone Disorders in Chronic Kidney Disease: An Update in Diagnosis and Management.

Renal osteodystrophy (ROD) is a bone disorder that occurs in chronic kidney disease (CKD) patients and is associated with 2- to 14-fold increased fracture risk compared to the general population. Risk of fractures is also increased in kidney transplant recipients especially within the first 5 years after transplantation. Fractures in CKD patients are associated with increased morbidity and mortality; thus, proper screening and management of CKD bone complications is critical to improving clinical outcomes. Tetracycline double-labeled transiliac crest bone biopsy with histomorphometry is the gold standard for the diagnosis and classification of ROD. However, bone biopsy is not practical to obtain in all patients. Thus, there is great interest in noninvasive approaches that can be used in the clinic to assess ROD. Here, we discuss the role of surrogate measures of bone health in CKD patients, such as dual energy X-ray absorptiometry (DXA) and novel high-resolution imaging, in conjunction with biochemical biomarkers of bone turnover. Recommended guidelines for diagnosis and management of CKD-MBD are discussed.

Can one evaluate bone disease in chronic kidney disease without a biopsy?

PURPOSE OF REVIEW: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complex disorder of bone and mineral metabolism that results in an excess risk of fractures, cardiovascular events and mortality. The management of the bone disorder aspect of CKD-MBD may require bone biopsy to determine appropriate treatment strategies. However, it is unclear when biopsy may be necessary and whether or not state-of-the art imaging and serologic testing can supplant the bone biopsy as a tool to assist with management decisions. RECENT FINDINGS: Advances in imaging methods now permit the noninvasive assessment of structural aspects of bone quality. Furthermore, common bone imaging tools, such as dual-energy X-ray absorptiometry, can be used to stratify for fracture risk. Circulating markers of bone turnover can be used to assess the risk of bone loss and fracture, but they are less useful in diagnosing the type of renal osteodystrophy. SUMMARY: Although advances in imaging now permit the assessment of fracture risk more accurately in CKD patients, the assessment of the type of renal osteodystrophy remains poor without bone biopsy. The virtual bone biopsy will be possible only when we are able to noninvasively assess turnover with good accuracy. A bone biopsy is needed when the bone turnover is unclear.

Trimethoprim-associated hyponatremia.

Hyponatremia associated with diuretic use can be clinically difficult to differentiate from the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We report a case of a 28-year-old man with HIV (human immunodeficiency virus) and Pneumocystis pneumonia who developed hyponatremia while receiving trimethoprim-sulfamethoxazole (TMP/SMX). Serum sodium level on admission was 135 mEq/L (with a history of hyponatremia) and decreased to 117 mEq/L by day 7 of TMP/SMX treatment. In the setting of suspected euvolemia and Pneumocystis pneumonia, he was treated initially for SIADH with fluid restriction and tolvaptan without improvement in serum sodium level. A diagnosis of hyponatremia secondary to the diuretic effect of TMP subsequently was confirmed, with clinical hypovolemia and high renin, aldosterone, and urinary sodium levels. Subsequent therapy with sodium chloride stabilized serum sodium levels in the 126- to 129-mEq/L range. After discontinuation of TMP/SMX treatment, serum sodium, renin, and aldosterone levels normalized. TMP/SMX-related hyponatremia likely is underdiagnosed and often mistaken for SIADH. It should be considered for patients on high-dose TMP/SMX treatment and can be differentiated from SIADH by clinical hypovolemia (confirmed by high renin and aldosterone levels). TMP-associated hyponatremia can be treated with sodium supplementation to offset ongoing urinary losses if the TMP/SMX therapy cannot be discontinued. In this Acid-Base and Electrolyte Teaching Case, a less common cause of hyponatremia is presented, and a stepwise approach to the diagnosis is illustrated.

Association of race and body mass index with ESRD and mortality in CKD stages 3-4: results from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: A recent cross-sectional analysis of Kidney Early Evaluation Program (KEEP) participants suggested that obesity is a heterogeneous disease state in African Americans and whites with chronic kidney disease (CKD). STUDY DESIGN: In longitudinal analyses spanning 8 years of follow-up, we examined whether race and body mass index (BMI) influence end-stage renal disease (ESRD) and mortality rates in participants with CKD stages 3-4. SETTING & PARTICIPANTS: KEEP participants were included in this analysis if they met the following criteria: (1) estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2), (2) white or African American race, and (3) no previous dialysis or transplantation. OUTCOMES & MEASUREMENTS: Survival analyses were performed for the outcomes of ESRD, death, and combined outcome of ESRD or death. RESULTS: Of 14,631 participants with CKD stages 3-4, 28% were African American and 72% were white. African American participants had higher rates of obesity and hypertension, with a higher baseline mean eGFR, higher prevalence of albuminuria, and greater degree of anemia compared with whites. In multivariable models, African American race increased the risk of ESRD (HR, 1.66; 95% CI, 1.26-2.07), but not death (HR, 0.89; 95% CI, 0.76-1.03). In these models, male sex, hypertension, diabetes, lower baseline eGFR, and albuminuria were predictive of higher rates of ESRD; age, male sex, diabetes, lower baseline eGFR, and albuminuria were predictive of overall mortality. There was no significant interaction between race and BMI in the adjusted model for outcomes of ESRD (P = 0.7) or death (P = 0.3). LIMITATIONS: Baseline values used in the analysis are from a cross-sectional data set. Dyslipidemia and secondary hyperparathyroidism were not accounted for in the analysis. CONCLUSIONS: African American race was associated with a higher incidence of ESRD, but not mortality. Although obesity may be a heterogeneous disease state in African Americans and whites with CKD, there does not appear to be a significant interaction between race and BMI in progression to ESRD or death.

Utility of the digital rectal examination in the evaluation of undifferentiated abdominal pain.

OBJECTIVE: The digital rectal examination (DRE) is commonly recommended in the evaluation of individuals with undifferentiated abdominal pain (UAP) despite negligible evidence. We aimed to determine its clinical utility. METHODS: We prospectively enrolled 893 UAP subjects in an observational, convenience sample study at our urban, academic emergency department. Exclusion criteria were age younger than 18 years, vaginal or rectal bleeding, pregnancy, and primarily flank pain or vaginal complaint. Data forms were completed before laboratory testing, imaging, or other diagnostic maneuvers; and structured telephone and chart follow-up was performed. Physicians were asked to document DRE findings contemporaneously as well as their perception of the DRE's diagnostic impact. Final diagnosis in each case was compared with DRE result. RESULTS: Five hundred thirty-eight of 893 (60%) subjects had a DRE performed at the discretion of the examining physician. The DRE was classified as "not useful" in 494 of 538 (92%). In the remaining 44 subjects, physicians reported having their differential diagnosis influenced by the DRE. Seventeen of 538 (3%; 0.95 confidence interval, 1.9%-5.0%) were diagnostically helped, and 12 of 538 (2%; 0.95 confidence interval, 1.3%-3.9%) were diagnostically harmed. Eleven of 538 (2%) were lost to final follow-up. Sensitivity analysis indicates that unless all 11 had diagnostically helpful DREs, the DRE was statistically as likely to be harmful as helpful. CONCLUSION: Differential diagnosis was unaffected in most subjects undergoing DRE, and it appears as likely to be harmful as helpful in predicting final diagnosis. Given the discomfort and minimal predictive value of the DRE in this setting, highly selective use seems reasonable.