Determinants of the serum phosphate concentration in chronic kidney disease.

If Ccr is creatinine clearance and EP and TRP are rates of phosphate excretion and reabsorption, the serum phosphate concentration (Ps) is the sum of EP/Ccr and TRP/Ccr, i.e., the amounts of phosphate excreted and reabsorbed per volume of filtrate. At equilibrium, influx of phosphate into plasma determines EP, and EP/Ccr quantifies the contribution of phosphate influx to Ps. We used data obtained at 688 clinic visits of 387 patients to analyze the evolution of Ps in chronic kidney disease (CKD) stages G1 - 5 (dialysis excluded). EP/Ccr was calculated as (Pu×crs)/cru and TRP/Ccr as Ps-EP/Ccr (where u is urine, s is serum, and cr is creatinine). Means of these parameters were plotted against CKD stages, and correlations among variables were determined with regression analyses. In comparison to values in CKD stages G1 - 2, EP/Ccr rose and TRP/Ccr fell by the same amount in CKD G3a and G3b, and Ps did not change. In stages G4 and G5, EP/Ccr increased sharply, TRP/Ccr fell minimally, and Ps rose significantly. At estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m2, TRP/Ccr was the principal determinant of Ps at eGFR < 45 mL/min/1.73m2, contributions of EP/Ccr and TRP/Ccr to Ps were comparable. Taken together, our results show that in CKD stages G4 and G5, the effect of phosphate reabsorption on Ps changes negligibly while that of phosphate influx increases dramatically. Because the tubular response to rising EP/Ccr is limited, maintenance of stable Ps in advanced CKD requires extreme reduction of phosphate influx into plasma. TRP/Ccr may define the lowest attainable Ps.

Awareness and knowledge among internal medicine house-staff for dose adjustment of commonly used medications in patients with CKD.

BACKGROUND: Drug dosing errors result in adverse patient outcomes and are more common in patients with chronic kidney disease (CKD). As internists treat the majority of patients with CKD, we study if Internal Medicine house-staff have awareness and knowledge about the correct dosage of commonly used medications for those with CKD. METHODS: A cross-sectional survey was performed and included 341 participants. The outcomes were the awareness of whether a medication needs dose adjustment in patients with CKD and whether there was knowledge for the level of glomerular filtration rate (GFR) a medication needs to be adjusted. RESULTS: The overall pattern for all post-graduate year (PGY) groups in all medication classes was a lack of awareness and knowledge. For awareness, there were statistically significant increased mean differences for PGY2 and PGY3 as compared to PGY1 for allergy, endocrine, gastrointestinal, and rheumatologic medication classes but not for analgesic, cardiovascular, and neuropsychotropic medication classes. For knowledge, there were statistically significant increased mean differences for PGY2 and PGY3 as compared to PGY1 for allergy, cardiovascular, endocrine, and gastrointestinal, medication classes but not for analgesic, neuropsychotropic, and rheumatologic medication classes. CONCLUSIONS: Internal Medicine house-staff across all levels of training demonstrated poor awareness and knowledge for many medication classes in CKD patients. Internal Medicine house-staff should receive more nephrology exposure and formal didactic educational training during residency to better manage complex treatment regimens and prevent medication dosing errors.

Fulminant hepatic failure with virtually undetectable serum alkaline phosphatase.

Wilson's disease presenting as fulminant hepatic failure is a rare presentation that carries a high morbidity and mortality. We report a young patient who developed fulminant hepatic failure as the initial manifestation of Wilson's disease. Virtually undetectable serum alkaline phosphatase provided the first clue to the diagnosis. Our patient underwent a successful liver transplantation which is the only effective treatment in patients with Wilsonian fulminant hepatic failure. In this report, we discuss laboratory clues to the diagnosis of this form of Wilson's disease. Clinicians should have a high suspicion of Wilson's disease as any delay in diagnosis can be catastrophic.

Changes in osmol gap in chronic kidney disease: an exploratory study.

AIM: There is no data on osmol gap (OG) in chronic kidney disease (CKD) by stage and limited data on OG in adults on maintenance hemodialysis (HD). We aimed to examine the OG between different stages of CKD and to compare the OG pre- and post-HD in those on maintenance HD. METHODS: We conducted a cross-sectional study of 67 patients. The participants were divided into six groups: Group 1-reference group (normal renal function), Group 2-CKD stage 2; Group 3-CKD stage 3; Group 4-CKD stage 4; Group 5-CKD stage 5 and not on dialysis. Group 6 were subjects on maintenance HD. RESULTS: The means of OG ± standard deviation of Groups 1-6 were 15.25 ± 3.0, 20.73 ± 2.68, 22.85 ± 6.99, 24.11 ± 3.64, 25.15 ± 5.06, and 28.88 ± 3.45, respectively (p < 0.001). In the HD group, the difference between the pre-HD and post-HD OG was statistically significant (p < 0.001). CONCLUSION: There is a statistically significant upward trend for OG as CKD stage increases. The OG is elevated in patients on maintenance HD and is normalized by the HD. OG can be a valuable additional tool to suggest CKD stage and serve as a marker of dialysis adequacy.

Treatment of severe hyponatremia with continuous renal replacement therapy: A case and review of corrective strategies.

Treatment of severely hyponatremic patients with continuous renal replacement therapy (CRRT) presents a unique challenge given the lack of commercial options for hypotonic replacement solutions or dialysate. We report the case of a 55-year-old male who presented with profound, symptomatic hyponatremia in the setting of acute kidney injury (AKI). The patient was found to have a serum sodium concentration of 97 mEq/L because of free water retention that occurred during severe AKI from viral gastroenteritis and rhabdomyolysis. Continuous veno-venous hemofiltration (CVVH) was required for AKI complicated by hyperkalemia, metabolic acidosis, and uremia. To prevent overcorrection of serum sodium, replacement fluids customized to natremic status had to be prepared. Conventional replacement fluid was modified on a daily basis to create hypotonic solutions with successively higher sodium concentrations. Over the course of a week, serum sodium successfully improved in a controlled and safe fashion. This case incorporates and reviews the variety of methods that have been used to safely manage severe hyponatremia with CRRT.

Effect of intensive blood pressure on the progression of non-diabetic chronic kidney disease at varying degrees of proteinuria.

The ideal blood pressure (BP) target for renoprotection is uncertain in patients with non-diabetic chronic kidney disease (CKD), especially considering the influence exerted by pre-existing proteinuria. In this pooled analysis of landmark trials, we coalesced individual data from 5001 such subjects randomized to intensive versus standard BP targets. We employed multivariable regression to evaluate the relationship between follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CKD progression (defined as glomerular filtration rate decline by 50% or end-stage renal disease), focusing on the potential for effect modification by baseline proteinuria or albuminuria. The median follow-up was 3.2 years. We found that SBP rather than DBP was the primary predictor of renal outcomes. The optimal SBP target was 110-129 mm Hg. We observed a strong interaction between SBP and proteinuria such that lower SBP ranges were significantly linked with progressively lower CKD risk in grade A3 albuminuria or ≥0.5-1 g/day proteinuria (relative to SBP 110-119 mm Hg, the adjusted HR for SBP 120-129 mm Hg, 130-139 mm Hg, and 140-149 mm Hg was 1.5, 2.3, and 3.3, respectively; all p<0.05). In grade A2 microalbuminuria or proteinuria near 0.5 g/day, a non-significant but possible connection was seen between tighter BP and decreased CKD (aforementioned HRs all <2; all p>0.05), while in grade A1 albuminuria or proteinuria <0.2 g/day no significant association was apparent (HRs all <1.5; all p>0.1). We conclude that in non-diabetic CKD, stricter BP targets <130 mm Hg may help limit CKD progression as proteinuria rises.

Systemic Bartonellosis Manifesting With Endocarditis and Membranoproliferative Glomerulonephritis.

Cat scratch disease caused by Bartonella species is mostly benign and self-limiting condition. Systemic infection is uncommon in immunocompetent host. We describe the case of a 66-year-old male who presented with sudden painless left eye blindness and brown-colored urine. Laboratory findings revealed progressively rising serum creatinine in association with nephrotic-range proteinuria at 7 g/day and glomerular hematuria on urinalysis. An echocardiogram demonstrated mitral and tricuspid valve vegetations despite multiple negative blood cultures. The left eye blindness was attributed to retinal artery occlusion from septic valvular embolus. Kidney biopsy showed membranoproliferative glomerulonephritis pattern of injury with "full house" pattern on immunofluorescent staining with subendothelial deposits on electron microscopy. Markedly elevated IgG (immunoglobulin G) titers for B henselae and B quintana were discovered. The patient had several cats at home. Kidney failure rapidly progressed to require hemodialysis. Once the diagnosis of systemic bartonellosis was confirmed, doxycycline (for 4 months) with rifampicin (for 3 months) were initiated. Repeat echocardiogram in 4 months demonstrated a resolution of valvular vegetations; however, the left eye blindness was permanent. In the present case the correct diagnosis of systemic bartonellosis allowed institution of appropriate antibiotic therapy and to also achieve a partial recovery of renal function and to discontinue hemodialysis.

Hemodialysis-associated soft tissue amyloidomas of the chest and abdominal wall.

Amyloidoma is a highly unusual presentation of amyloidosis in tumoral or nodular form. Isolated soft tissue amyloidomas in individuals with end-stage renal disease on chronic hemodialysis is exceedingly rare, particularly in the era of advanced dialysis technologies. We report the case of a 55-year-old male with end-stage renal disease due to autosomal-dominant polycystic kidney disease, on HD for over 30 years, who was found to have soft-tissue, dialysis-related (ß2 -microglobulin) amyloidomas (DRA). He presented with painful, palpable masses within the thoracic and abdominal walls. Serum ß2 -microglobulin level was only mildly elevated at 24.9 mg/L. Biopsy confirmed amyloidosis with positivity for Congo Red staining and apple-green birefringence under polarized light. Amyloid subtyping with immunohistochemistry showed positive ß2 -microglobulin staining within the deposits. Conservative therapy involving pain management and close monitoring resulted in eventual improvement in symptoms and thus proved to be a viable option for treatment.

Oligosecretory Myeloma With Amyloidosis and Alopecia.

Amyloidosis is a systemic illness characterized by the extracellular deposition of abnormal proteins in body tissues and organs. In addition to renal involvement, amyloidosis can also present with a variety of skin manifestations, though rarely with alopecia. Sixteen cases of alopecia secondary to systemic amyloidosis are reported. There is one reported case that presented with alopecia universalis. We report a case of a 68-year-old woman presenting with alopecia universalis, rapid decline in kidney function, and nephrotic syndrome who was found to have multiple myeloma-associated AL amyloidosis (immunoglobulin light chain). Her serological workup including serum electrophoresis was negative and she underwent renal biopsy. Pathology revealed eosinophilic material within the mesangium that was Congo-red positive, had apple-green birefringence under polarized light, and ultramicroscopically appeared as fibrillary material. Subsequent bone marrow examination showed a diffuse increase in plasma cells with atypia indicating plasma cell neoplasm. This case underlines several interesting aspects of multiple myeloma and the way it may present with amyloidosis. The lack of monoclonal spike on electrophoresis yet positive light chain analysis deserves special attention by clinicians to avoid a missed diagnosis. The extensive skin involvement also raises several questions regarding the pathologic mechanisms of alopecia in a patient with amyloidosis.

Antihypertensive therapy in nondiabetic chronic kidney disease: a review and update.

Hypertension is an important contributor to progression of nondiabetic chronic kidney disease (CKD). Compelling observational evidence indicates that the divergence of blood pressure (BP) away from an ideal range in either direction is associated with a progressive rise in the risk of mortality and cardiovascular and renal disease progression. To date, various clinical trials and meta-analyses examining strict versus less intensive BP control in nondiabetic CKD have not conclusively demonstrated a renal advantage of one BP-lowering approach over another, except in certain subgroups such as proteinuric patients where evidence is circumstantial. As recent data have come to light suggesting that intensive BP control yields superior survival and cardiovascular outcomes in patients at high risk for cardiovascular disease, interest in the prospect of whether such benefit extends to individuals with CKD has surged. This review is a comprehensive analysis of antihypertensive literature in nondiabetic renal disease, with a particular emphasis on BP target.