An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism.

AIMS: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism (sHPT), but the bone histologic response has not been described. This prospective, double-blind, placebo-controlled trial assessed the effects of cinacalcet on bone histology and serum markers of bone metabolism in dialysis patients with sHPT. METHODS: Patients with intact PTH (iPTH) > or = 300 pg/ml were randomly assigned 2:1 to receive cinacalcet or placebo with concurrent vitamin D and/or phosphate binder therapy. Cinacalcet (30 - 180 mg/day) was used to achieve iPTH levels < or = 200 pg/ml. Bone biopsies were performed before and after one year of treatment. RESULTS: Baseline and end-of-study data were available from 32 patients (19 cinacalcet, 13 placebo). Baseline bone turnover was elevated in 27, reduced in 3 and normal in 2 patients. Serum bone-specific alkaline phosphatase (BSAP) and N-telopeptide (NTx) were elevated. Cinacalcet treatment decreased PTH and diminished activation frequency, bone formation rate/bone surface, and fibrosis surface/bone surface. Adynamic bone was observed in three patients receiving cinacalcet; in two of these, PTH levels were persistently low (< 100 pg/ml). The histomorphometric parameter changes in bone corresponded to PTH, BSAP and NTx reductions. Bone mineralization parameters remained normal. CONCLUSIONS: Treatment with cinacalcet lowered PTH and reduced bone turnover and tissue fibrosis among most dialysis patients with biochemical evidence of sHPT.

A comparative study of continuous ambulatory peritoneal dialysis and center hemodialysis. Efficacy, complications, and outcome in the treatment of end-stage renal disease.

We retrospectively compared 92 patients treated with center hemodialysis (CHD) and 72 patients receiving continuous ambulatory peritoneal dialysis (CAPD) over a 26-month period. The groups were comparable with respect to underlying disease and demographic characteristics. Biochemical control was also similar, with higher bicarbonate levels and hematocrits in patients receiving CAPD, despite fewer transfusions and minimal administration of anabolic steroid and iron therapy. Hospitalization rates were also similar (1.58 +/- 2.89 vs 1.43 +/- 3.35 days per patient month for patients receiving center hemodialysis vs CAPD, respectively). Access complications were the most frequent cause of hospitalization in both groups, but cardiovascular causes were more frequent among patients receiving CHD. Diabetic patients had significantly higher hospitalization rates, which were similar in both groups. Twenty-nine percent of the peritonitis episodes necessitated hospitalization. Mortality and dropout rates were virtually identical in the two groups, with a 70% retention rate during the 26-month study. Continuous ambulatory peritoneal dialysis is comparable with CHD with regard to biochemical results, complications, hospitalization rates, and outcome. It is widely applicable, as 44% of our new patients with end-stage renal disease are being sent home receiving this treatment.

Amyloidosis secondary to drug abuse and chronic skin suppuration.

Amyloidosis has not been included in the wide spectrum of medical complications associated with drug abuse. Chronic visceral infection is a recognized cause of amyloidosis, but chronic suppuration of the skin is not a well-appreciated cause of this condition. Furthermore, to our knowledge, chronic skin suppuration secondary to parenteral drug abuse has not been reported as a cause for systemic amyloidosis. We report a case in which subcutaneous injections of narcotic tablets led to chronic skin suppuration and systemic amyloidosis.

Nondilated obstructive nephropathy.

Three patients had renal failure due to obstructive nephropathy associated with processes that prevented dilatation of the collecting systems. Thus, various radiologic procedures, including renal sonography, angiography, and isotope renography, all failed to identify an obstructing process. Because of the high index of clinical suspicion, surgical exploration and nephrostomy were performed on each patient. This confirmed the presence of obstructive nephropathy and led to marked improvement of renal function in each case. When renal failure develops in a setting with a high probability of ureteral obstruction, this diagnosis should be vigorously pursued despite normal radiologic results.

Salt-wasting bronchorrhea and its mechanisms.

A 56-year old woman, with the diffuse form of bronchioloalveolar cell carcinoma, developed massive bronchorrhea, resulting in severe fluid and electrolyte depletion when her oral intake was compromised. Chemical analysis of the bronchial secretions and the ultrastructural features of the tumor cells support the concept of an active secretory process. The lactic dehydrogenase (LDH) isoenzyme pattern of the fluid is similar to that found in fetal cells. The neoplastic cells may acquire a more primitive LDH pattern.

Subclavian vein stenosis as a complication of subclavian catheterization for hemodialysis.

Thirteen patients had placement of a subclavian vein catheter for temporary vascular access for hemodialysis. Peripheral venography was performed within two to six weeks of catheter placement. Forty-six percent (six of 13 patients) developed subclavian vein narrowing, which resolved in two patients. The duration of catheter placement had no impact on the incidence of this complication. Subclavian vein catheterization can frequently lead to subclavian vein stenosis, which often will resolve spontaneously. Consideration should be given to placement of subclavian lines on the contralateral side of a planned permanent vascular access.

Role of the nephrologist in the intensive care unit.

Intensive care units (ICUs) are increasingly becoming a focal point for tension between medical specialists. In an extreme approach to this issue, some ICUs have become closed units managed by intensivists, with other specialists, such as nephrologists, having a restricted supportive role. The nephrologist, a subspecialist with broad skills in general internal medicine, has trained and appropriately can serve as the primary physician for patients with significant renal failure and end-stage renal disease in multiple hospital settings, including the ICU. Sick and complex hospitalized patients offer ample opportunity for a collaborative interaction between the nephrologist and intensivist in the ICU.

Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial.

Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial.

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study.

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.

Potential angiotensin-converting enzyme inhibitor-epoetin alfa interaction in patients receiving chronic hemodialysis.

We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (+/- SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 +/- 2575, 5800 +/- 2026, and 5660 +/- 2285 U 3 times/week (p=0.56), and mean differences were -212 U for 0-3 months (95% CI -1310 to 886) and -713 U for 0-12 months (95% CI -2142 to 716). Mean +/- SD hematocrits were 30.5 +/- 3.9%, 31.6 +/- 3.2%, and 34.2 +/- 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0-3 months (95% CI -1.41 to 4.81) and 3.85% for zero-12 months (95% CI 0.71-7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.

Acute interstitial nephritis secondary to infectious mononucleosis.

Renal involvement in infectious mononucleosis (IM) is infrequent. In most cases it is self-limited and is rarely associated with loss of renal function. The purpose of this case report is to document a case of acute interstitial nephritis (AIN) leading to acute renal failure (ARF) in a patient with Epstein-Barr virus (EBV) infection and to review literature of EBV infection and its renal manifestation. The patient was managed with hemodialysis and steroids and made an uneventful recovery. Renal involvement in IM may be more common than generally appreciated and may occasionally lead to ARF. Therapy with corticosteroids may have role in the management of IM-induced ARF and may shorten the duration of renal failure.

Dialysis adequacy in hypoalbuminemic continuous ambulatory peritoneal dialysis patients.

We examined the interrelationship between hypoalbuminemia (HA) and the normalized protein catabolic rate (NPCR; g/kg/day) in the face of adequate Kt/V and weekly creatinine clearances in 40 end-stage renal disease patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We also evaluated serum albumin (SA) levels as an additional marker of nutritional status of the PD patients receiving adequate dialysis therapy in terms of Kt/V greater than 1.5 per week. Twenty-three of 40 patients had normal serum albumin (NSA; > or = 3.4 g/dL) and 17 had HA (< g/dL). A correlation between NPCR and SA levels was observed. Also, the NPCR values in patients with NSA (0.98 +/- 0.31) differ significantly (p < 0.0005) from patients with HA (0.80 +/- 0.13). Urea kinetic parameters for adequacy of dialysis, that is, Kt/V, blood urea nitrogen (BUN), and weekly creatinine clearance, did not reveal any statistically significant difference between patients with NSA and HA. These data suggest that low values of NPCR may be seen in hypoalbuminemic CAPD patients despite adequate dialysis therapy and indicate further investigation for associated morbid conditions or supplemental nutrition.

Dialysis adequacy versus metabolic factors in the clinical assessment of CAPD.

We performed a cross sectional study of our continuous ambulatory peritoneal dialysis (CAPD) patients (n = 98) to examine the relation between parameters of adequacy of dialysis [KT/V, weekly creatinine clearance (Ccr)], urea kinetics (PCR), biochemical parameters (serum albumin), and clinical status of these patients. We also investigated the predictive value of these parameters in the determination of clinical outcomes. The clinical status of each patient was assessed by patient self-assessment and objectively by physicians and nurses. On this basis a total clinical assessment score was assigned. Individuals with a score of 3 or less were judged to be clinically stable (group 1, n = 61), while a score of 4 or more was considered "not doing well" (group 2, n = 37). A good correlation (r = 0.7) between subjective and objective assessments was observed. No correlation between total clinical assessment score and KT/V, PCRN (normalized protein catabolic rate), or Ccr was obtained, while serum albumin levels correlated inversely (r = -0.30; p < 0.003), suggesting that parameters of dialysis adequacy (weekly KT/V, Ccr) and urea kinetics (PCRN) are not predictive of clinical outcome in CAPD patients, in contrast with hemodialysis (HD) patients. Serum albumin levels were observed to be correlated with clinical outcome in CAPD patients. Hypoalbuminemia was observed in group 2 patients, despite statistically insignificant different values of KT/V, Ccr, and PCRN in the two groups. Therefore, clinical assessment and parameters such as serum albumin must be considered when determining the total well-being of CAPD patients.