Hypomagnesemia in critically ill cancer patients: a prospective study of predictive factors

Hypomagnesemia is the most common electrolyte disturbance seen upon admission to the intensive care unit (ICU). Reliable predictors of its occurrence are not described. The objective of this prospective study was to determine factors predictive of hypomagnesemia upon admission to the ICU. In a single tertiary cancer center, 226 patients with different diagnoses upon entering were studied. Hypomagnesemia was defined by serum levels <1.5 mg/dl. Demographic data, type of cancer, cause of admission, previous history of arrhythmia, cardiovascular disease, renal failure, drug administration (particularly diuretics, antiarrhythmics, chemotherapy and platinum compounds), previous nutrition intake and presence of hypovolemia were recorded for each patient. Blood was collected for determination of serum magnesium, potassium, sodium, calcium, phosphorus, blood urea nitrogen and creatinine levels. Upon admission, 103 (45.6%) patients had hypomagnesemia and 123 (54.4%) had normomagnesemia. A normal dietary habit prior to ICU admission was associated with normal Mg levels (P = 0.007) and higher average levels of serum Mg (P = 0.002). Postoperative patients (N = 182) had lower levels of serum Mg (0.60 ± 0.14 mmol/l compared with 0.66 ± 0.17 mmol/l, P = 0.006). A stepwise multiple linear regression disclosed that only normal dietary habits (OR = 0.45; CI = 0.26-0.79) and the fact of being a postoperative patient (OR = 2.42; CI = 1.17-4.98) were significantly correlated with serum Mg levels (overall model probability = 0.001). These findings should be used to identify patients at risk for such disturbance, even in other critically ill populations.

ClC-5 chloride channel and kidney stones: what is the link?

Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.

Anti-leishmania antibodies in cerebrospinal fluid from dogs with visceral leishmaniasis

Visceral leishmaniasis in Brazil is caused by Leishmania (Leishmania) chagasi and the dog is its most important reservoir. The clinical features in dogs include loss of weight, lymphadenopathy, renal failure, skin lesions, fever, hypergammaglobulinemia, hepatosplenomegaly, anemia, and, rarely, neurological symptoms. Most infected animals develop active disease, characterized by high anti-leishmania antibody titers and depressed lymphoproliferative ability. Antibody production is not primarily important for protection but might be involved in the pathogenesis of tissue lesions. An ELISA test was used to determine if there is an association between neurological symptoms and the presence of anti-L. chagasi antibodies in cerebrospinal fluid (CSF). Thirty serum and CSF samples from symptomatic mixed breed dogs (three with neurological symptoms) from a region of high incidence of visceral leishmaniasis in Brazil were examined for antibody using total parasite antigen and anti-dog IgG peroxidase conjugate. A high level of L. chagasi antibodies was observed in sera (mean absorbance ± SD, 1.939 ± 0.405; negative control, N = 20, 0.154 ± 0.074) and CSF (1.571 ± 0.532; negative control, N = 10, 0.0195 ± 0.040) from all animals studied. This observation suggests that L. chagasi can cause breakdown of filtration barriers and the transfer of antibodies and antigens from the blood to the CSF compartment. No correlation was observed between antibody titer in CSF and neurological symptoms.

Factors associated with penicillin-nonsusceptible pneumococcal infections in Brazil

Resistance of Streptococcus pneumoniae is a worldwide, growing problem. Studies of factors associated with resistance to penicillin have not been conducted in Brazil. The objective of the present study was to evaluate factors associated with infection by S. pneumoniae not susceptible to penicillin. A prevalence study was conducted including all patients with a positive culture for S. pneumoniae in a hospital from July 1991 to December 1992 and the year 1994. Of 165 patients identified, 139 were considered to have clinically relevant infections and 88% of them had invasive infections. All infections were community acquired and consisted of pneumonia (44%) and of central nervous system (19%), pelvic or abdominal (12%), upper airway or ocular (12%), primary bloodstream (9%) and skin and soft tissue (5%) infections. Mortality was 25%. Susceptibility to penicillin was present in 77.6% of the isolates; 21.8% were relatively resistant, and one isolate was resistant (minimal inhibitory concentration = 4 µg/ml). Multivariate analysis showed that age below 4 years (odds ratio (OR): 3.53, 95% confidence interval (95%CI): 1.39-8.96) and renal failure (OR: 5.50, 95%CI: 1.07-28.36) were associated with lack of susceptibility to penicillin. Bacteremia occurred significantly less frequently in penicillin-nonsusceptible infections (OR: 0.34, 95%CI: 0.14-0.84), possibly suggesting that lack of penicillin susceptibility is associated with lower virulence in S. pneumoniae.

Comparative study of IgA nephropathy with and without crescents

Glomerular crescents were analyzed as a prognostic factor in retrospectively reviewed data from 144 patients with biopsy-proven IgA nephropathy. Crescents were found in 26 (18%) patients, and detected in 2 to 100% of glomeruli in each specimen. In 5% of the patients more than 50% of the glomeruli were affected. Thirty patients with IgA nephropathy without crescents were studied as a control group. Mean age was 30.3 ± 9.4 and 30.2 ± 12.0 years for the patients with and without crescents, respectively, and males prevailed in both groups. The length of follow-up was 23.2 ± 41.6 months for patients with crescents and 29.3 ± 35.3 months for patients without crescents. Eighty percent of the patients with crescents were hypertensive, compared to 27% of the non-crescent control group (P < 0.05). Mean serum creatinine at the time of diagnosis was 3.9 ± 2.9 and 1.9 ± 2.1 mg/dl for the patients with and without crescents, respectively. Initial urinary protein excretion was higher in patients with crescents (4.6 ± 3.5 vs 1.2 ± 0.9 g/day; P < 0.05). At the end of follow-up 17 patients (77.3%) from the crescent group and 3 (11.1%) from the non-crescent group had end-stage renal disease (P < 0.0001). The presence of crescents was associated with higher levels of initial serum creatinine and urinary protein excretion, and a higher frequency of hypertension and progression to end-stage renal disease.

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age ± SD: 51.3 ± 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (<100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (>280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Response of the growth plate of uremic rats to human growth hormone and corticosteroids

Children with chronic renal failure in general present growth retardation that is aggravated by corticosteroids. We describe here the effects of methylprednisolone (MP) and recombinant human growth hormone (rhGH) on the growth plate (GP) of uremic rats. Uremia was induced by subtotal nephrectomy in 30-day-old rats, followed by 20 IU kg-1 day-1 rhGH (N = 7) or 3 mg kg-1 day-1 MP (N = 7) or 20 IU kg-1 day-1 rhGH + 3 mg kg-1 day-1 MP (N = 7) treatment for 10 days. Control rats with intact renal function were sham-operated and treated with 3 mg kg-1 day-1 MP (N = 7) or vehicle (N = 7). Uremic rats (N = 7) were used as untreated control animals. Structural alterations in the GP and the expression of anti-proliferating cell nuclear antigen (PCNA) and anti-insulin-like growth factor I (IGF-I) by epiphyseal chondrocytes were evaluated. Uremic MP rats displayed a reduction in the proliferative zone height (59.08 ± 4.54 vs 68.07 ± 7.5 µm, P < 0.05) and modifications in the microarchitecture of the GP. MP and uremia had an additive inhibitory effect on the proliferative activity of GP chondrocytes, lowering the expression of PCNA (19.48 ± 11.13 vs 68.64 ± 7.9% in control, P < 0.0005) and IGF-I (58.53 ± 0.96 vs 84.78 ± 2.93% in control, P < 0.0001), that was counteracted by rhGH. These findings suggest that in uremic rats rhGH therapy improves longitudinal growth by increasing IGF-I synthesis in the GP and by stimulating chondrocyte proliferation.

Potential pathogenic role of aggregative- adhering Corynebacterium diphtheriae of different clonal groups in endocarditis

Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

Prognostic effect of high-flux hemodialysis in patients with chronic kidney disease

We investigated the prognostic effects of high-flux hemodialysis (HFHD) and low-flux hemodialysis (LFHD) in patients with chronic kidney disease (CKD). Both an electronic and a manual search were performed based on our rigorous inclusion and exclusion criteria to retrieve high-quality, relevant clinical studies from various scientific literature databases. Comprehensive meta-analysis 2.0 (CMA 2.0) was used for the quantitative analysis. We initially retrieved 227 studies from the database search. Following a multi-step screening process, eight high-quality studies were selected for our meta-analysis. These eight studies included 4967 patients with CKD (2416 patients in the HFHD group, 2551 patients in the LFHD group). The results of our meta-analysis showed that the all-cause death rate in the HFHD group was significantly lower than that in the LFHD group (OR=0.704, 95%CI=0.533-0.929, P=0.013). Additionally, the cardiovascular death rate in the HFHD group was significantly lower than that in the LFHD group (OR=0.731, 95%CI=0.616-0.866, P<0.001). The results of this meta-analysis clearly showed that HFHD decreases all-cause death and cardiovascular death rates in patients with CKD and that HFHD can therefore be implemented as one of the first therapy choices for CKD.

The long-term use of enalapril and hydrochlorothiazide in two novel mutations patients with Dent's disease type 1

Dent's disease type 1 is an X-linked tubular disease caused by mutations in the renal chloride channel CLCN-5, and it is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal failure. Several cases have been described in which the only presenting symptoms were asymptomatic proteinuria, and focal segmental or global glomerulosclerosis. The renal failure in these patients may be caused by hypercalciuria and persistent proteinuria. Therefore, angiotensin converse enzyme inhibitor and thiazides could be useful. Our aim is to report the effects of these drugs in two novel mutations patients with Dent's disease type 1. In this report, no significant correlations between dosage of hydrochlorothiazide and calciuria and no significant correlations between proteinuria and dosage of enalapril were detected. This is important since these are polyuric patients and these drugs could be dangerous to their renal function.

A case of late-onset oligomeganephronia

A 33-year old caucasian man was investigated for pain in the right flank, proteinuria, hemathuria and an elevated serum creatinine level. He also presented an abnormal ultrasonography, which revealed asymmetric kidneys. Through renal biopsy, the diagnosis of oligomeganephronia (OMN) was confirmed. OMN is a very rare form of renal hypoplasia, and late-onset in adulthood is even rarer. In the pediatric population, OMN leads to end-stage-renal-failure(ESRF) in a few years. This is the sixth case related in the literature of a late-onset OMN who have not yet developed ESRF.

Lipoprotein glomerulopathy: a case report of a rare disease in a brazilian child

Lipoprotein glomerulopathy (LPG) is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE) are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels.

Report of four cases of Bardet-Biedl syndrome

Bardet-Biedl syndrome is rare. Although its diagnosis depends on cardinal clinical manifestations which appear in childhood, we report four cases of Bardet-Biedl syndrome lately diagnosed in a dialysis center. Three cases were diagnosed in end-stage renal disease patients when they started maintenance hemodialysis, and one case was diagnosed through screening among hemodialysis patients' relatives. Although pediatricians have more opportunity to diagnose the syndrome, nephrologists are important during the treatment, since renal failure is the main cause of death among Bardet-Biedl syndrome patients. Moreover, late diagnosis of the syndrome among patients with end-stage renal disease can help to detect new cases through the screening among hemodialysis patients' relatives.

Five years results after intrafamilial kidney post-transplant in a case of familial hypomagnesemia due to a claudin-19 mutation

Introduction: Familial Hypomagnesaemia with hypercalciuria and nephrocalcinosis, with severe ocular impairment secondary to claudin-19 mutation, is a rare recessive autossomic disorder. Its spectrum includes renal Mg2+ wasting, medullary nephrocalcinosis and progressive chronic renal failure in young people. Objective: To report a case of kidney transplantation father to daughter in a familial occurrence of severe bilateral nephrocalcinosis associated with ocular impairment in a non-consanguineous Brazilian family, in which two daughters had nephrocalcinosis and severe retinopathy. Methods: The index case, a 19 years-old female, had long-lasting past medical history of recurrent urinary tract infections, and the abdominal X-ray revealed bilateral multiple renal calcifications as well as ureteral lithiasis, and she was under haemodialysis. She had the diagnosis of retinitis pigmentosa in the early neonatal period. The other daughter (13 years-old) had also nephrocalcinosis with preserved kidney function, retinopathy with severe visual impairment, and in addition, she exhibited hypomagnesaemia = 0.5 mg/dL and hypercalciuria. The other family members (mother, father and son) had no clinical disease manifestation. Mutation analysis at claudin-19 revealed two heterozygous missense mutations (P28L and G20D) in both affected daughters. The other family members exhibited mutant monoallelic status. In despite of that, the index case underwent intrafamilial living donor kidney transplantation (father). Conclusion: In conclusion, the disease was characterized by an autosomal recessive compound heterozygous status and, after five years of donation the renal graft function remained stable without recurrence of metabolic disturbances or nephrocalcinosis. Besides, donor single kidney Mg2+ and Ca2+ homeostasis associated to monoallelic status did not affect the safety and the usual living donor post-transplant clinical course.