Pathomorphology of kidney lesions induced by non-steroidal anti-inflammatory drugs

Pathomorphological findings on nephrobiopsies from two groups of patients with NSAID-induced kidney lesions are provided. In the first group (9 patients) the disease developed in patients of different age after short-term use of NSAID and was clinically manifested by acute renal failure with extrarenal allergic symptoms (skin, rash, eosinophilia). Morphological features were acute tubulo-interstitial nephritis without glomerular lesions. In the second group (23 patients) the disease developed after longterm use of NSAID in older patients with a compromised renal blood circulation presenting clinically with nephrotic syndrome, and morphologically by acute tubulo-interstitial nephritis with minimal change (lipoid nephrosis).     

Renal side-effects of non-steroidal antirheumatic drugs

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are increasingly used for analgesia, as antirheumatics and to inhibit platelet aggregation. Renal side effects occur mainly in patients at risk, e.g. those with pre-existing renal insufficiency, or when used together with diuretics or a second NSAID. PATIENTS: In these patients, reversible impairment of renal function, disturbance of electrolyte homeostasis, edema and hypertension are quite common. Nephrotic syndrome with or without interstitial nephritis and renal failure is a rare complication of long-term NSAID therapy. Analgesic nephropathy may result from chronic NSAID use. These three renal complications are exemplified by case reports. CONCLUSIONS: Since side effects of NSAIDs are initially reversible, careful observation of patients can prevent chronic illness. Only rarely dialysis or treatment with glucocorticoids is indicated in patients with interstitial nephritis. Given the large number of patients taking NSAIDs, however, renal side effects are rare, and usually have no long-term consequences. Nevertheless, early detection of side effects is of importance for the prevention of long-term medical complications.     

Severe hyperchloriduria-hyperkaliuria: a new congenital renal tubular abnormality?

A female infant, aged 5 weeks, had metabolic alkalosis associated with severe electrolyte disturbances. In addition to findings typically seen in patients with Bartter syndrome or hyperprostaglandin E syndrome, she had massive urinary excretion of prostaglandins E2 and E-M, normal calcium metabolism, hyperphosphaturia, and severe hyperchloriduria and hyperkaliuria with limited response to indomethacin. These findings may represent a new congenital renal tubular abnormality.     

Mutations in the ROMK gene in antenatal Bartter syndrome are associated with impaired K+ channel function

Children with the antenatal variant of Bartter syndrome present the typical pattern of impaired salt reabsorption in the thick ascending limb of Henle's loop (TALH) resulting in marked ante- and postnatal salt wasting. In some of these patients mutations in the renal potassium channel ROMK (KCNJ1) have been found. We analyzed the electrophysiological function of five recently described ROMK channel mutations (V72E, D108H, P110L, A198T and V315G). In whole cell patch clamp recordings wildtype rat ROMK1 exhibited K+ currents of >1 nA at a membrane potential of 100 mV when transfected into COS-7 kidney cells. These currents were sensitive to external Ba2+ and internal Mg2+, which are typical features of the inwardly rectifying KIR channel. In contrast mutated ROMK1 cDNAs expressed either no or only infrequently small currents (<200 pA). Loss of tubular K+ channel function probably prevents apical membrane potassium recycling with secondary inhibition of Na-K-2Cl-cotransport in the TALH. We conclude that mutations in the potassium channel ROMK are the primary events causing renal salt wasting in a subset of patients with the antenatal variant of Bartter syndrome.     

Effect of a nonsteroidal antiinflammatory drug on synovial fluid in osteoarthritis

OBJECTIVE: The use of nonsteroidal antiinflammatory drug (NSAID) therapy in osteoarthritis (OA) is controversial because of suggestions that pure analgesics can be as effective as NSAID for pain relief. In addition, there is incomplete information whether antiinflammatory effects have any longterm benefit in OA. NSAID have been known to affect synovial fluid (SF) prostaglandins in rheumatoid arthritis. We describe the first examination of the effect of an NSAID, etodolac, on SF prostaglandins, cytokines, and cells in OA. METHODS: Joint fluids were studied before and 2 weeks after initiation of therapy with etodolac 400 mg tid. Leukocyte counts, prostaglandin, interleukin 6, and tumor necrosis factor were measured. RESULTS: Pretreatment features of SF did not predict clinical response. We found no change in the relatively low leukocyte counts. However, SF prostaglandin levels and interleukin 6 levels were significantly decreased and tumor necrosis factor alpha levels were increased after therapy with NSAID. CONCLUSION: This NSAID had potentially important local effects that could be either beneficial or deleterious. Further studies on effects of this and other NSAID on a broader variety of SF and synovial cytokines may help predict longterm effects of NSAID on progression of OA.     

Renal autotransplantation for the loin pain-hematuria syndrome: long-term followup of 26 cases

PURPOSE: We review the long-term results of renal autotransplantation as a form of nephron sparing renal denervation for patients with the loin pain-hematuria syndrome. MATERIALS AND METHODS: From 1985 to 1997, after exclusion of other urological, nephrological and psychiatric causes for severe intractable flank pain and recurrent hematuria, 22 patients with severe debility and heavy narcotic dependency underwent 26 renal autotransplantations for pain control. Postoperative pain relief, narcotic use, level of function in daily activities and status of the autograft were assessed. RESULTS: Median and mean followup was 78.5 and 84.7 months (range 30 to 138), respectively. There were 2 technical failures. Pain recurred within 2 years after 6 procedures, of which 3 resulted in transplant nephrectomy and 3 were managed with a reduced analgesic requirement. Of the 16 patients with minimum 5 years of followup 12 (75%) were pain-free after surgery with 3 additional patients pain-free after transplant nephrectomy. Overall, 18 of the 26 autotransplant procedures (69.2%) resulted in pain relief, in some cases beyond 10 years, with patients returning to normal daily activities. CONCLUSIONS: Renal autotransplantation results in durable narcotic-free favorable results in the majority of meticulously screened loin pain-hematuria syndrome patients. Although some failures, which usually occur within 2 years after surgery, can be expected, autotransplantation is justified as a nephron sparing denervation therapy for select loin pain-hematuria syndrome patients.     

On the treatment of recurrent tonsillitis by vaccination

OBJECTIVE: To analyze the use of Cyclosporine (CyA) in nephrotic syndrome. METHODS: Thirty five children of mean age of 5.9 years with steroid dependent (n = 26) or steroid resistant (n = 9) primary nephrotic syndrome with normal renal functions and who received CyA were studied. CyA was used at a dosage of 6-7 mg/kg/day orally in two divided doses. The mean duration of therapy was 9.6 weeks. All received a minimum of 8 weeks of CyA therapy. In a few who received longer therapy, the dose was reduced to 4 mg/kg/day. All patients were monitored serially for hepatotoxicity and nephrotoxicity. The nephrotic state was evaluated serially with biochemical tests and followed up for a mean period of 2.55 years. RESULTS: Thirty one patients completed the study. The response to therapy was categorized into 5 groups-no response (4 patients), good response (4 patients), partial response (4 patients), cyclosporine dependence (16 patients), and infrequent relapsers (3 patients). Good response was defined as complete remission lasting for at least one year after cessation of therapy. Patients who showed partial response had reduction in quantitative proteinuria and needed less diuretics. Sixteen patients went into complete remission while on therapy but relapsed within 3 months of discontinuation (CyA dependence). The response to CyA correlated more with steroid-responsiveness than with the underlying histopathology. The drug was well tolerated. CONCLUSION: In steroid-dependent or steroid-resistant nephrotic children with normal renal functions, CyA therapy may be considered as one of the possible therapeutic options. Our results suggest that a longer duration of CyA therapy may possibly be indicated in these cases.     

Objectives to direct the training of emergency medicine residents on off-service rotations: surgery, Part 3

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Sch?nlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.     

Formulation and in vitro examination of furosemide containing suppositories and preliminary experiences of their clinical use

The renal sonographic findings in ten cases of Bartter s syndrome investigated at the King Khalid University Hospital, Riyadh, Saudi Arabia are described. There were various sonographic abnormalities other than those of hyperechoic pyramids as previously described. These were diffuse increased renal echogenicity and hyperechoic echogenicity in the kidneys with the exception of the pyramids. This condition can be suspected early if nephrocalcinosis is present in a child with a history of polyhydramnios and premature delivery.     

Wernicke's encephalopathy and dialysis: report of two cases

Wernicke encephalopathy is considered a complication of dialytic therapy, but there are few reports of this complication. We report a 57 years old man and a 45 years old woman, with grade IV renal failure, who after acute peritoneodialysis and chronic hemodialysis respectively, had a confusional syndrome that responded to the administration of thiamine. CT scans in both patients discarded abnormal blood collections or new cerebrovascular episodes. The man bad two previous cerebrovascular episodes, a severe anemia that was corrected, angina and an episode of arrhythmia during the dialytic procedure previous to the confusional episode. The woman had an acute uremic syndrome and a concomitant urinary tract infection during the confusional episode. Wernicke encephalopathy must be suspected in patients in dialysis with confusional episodes.     

Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome

Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13 families and have performed SSCP analysis of the coding sequence and the exon-intron boundaries of the NKCC2 gene; and we report 14 novel mutations in patients with antenatal Bartter syndrome, as well as the identification of three isoforms of human NKCC2 that arise from alternative splicing.     

Proteinuria, hypertension and chronic renal failure in X-linked Kallmann's syndrome, a defined genetic cause of solitary functioning kidney

BACKGROUND: Anosmia and hypogonadotrophic hypogonadism are the classic features of X-linked Kallmann's syndrome, a disorder caused by mutations of KAL, a gene expressed during kidney and brain development. About a third of patients have a solitary functioning kidney, but little is known about their renal morbidity. METHODS: We studied seven patients aged 22-35 years with X-linked Kallmann's syndrome and a solitary functioning kidney. RESULTS: Two patients developed significant proteinuria associated with mild to moderate arterial hypertension in the second to third decades of life. In one, proteinuria and renal impairment preceded the appearance of hypertension, and the disorder progressed to chronic renal failure. The remaining five patients had normal plasma creatinine concentrations and no significant proteinuria although four had borderline systolic and/or diastolic hypertension. In two sets of patients from the same kindreds, there was a striking discordance for the occurrence of renal morbidity. CONCLUSIONS: All patients with X-linked Kallmann's syndrome should be screened for renal malformations, and those with solitary kidneys require life-long follow-up to detect hypertension, proteinuria and renal failure.     

Kidney transplantation after a severe form of pseudotumor cerebri

Pseudotumor cerebri is a syndrome characterized by intracranial hypertension (intracranial pressure >200 mmH2O) and a normal ventricular system. The diagnosis should be made as early as possible to prevent impairment of vision. Several diseases have been reported in association with pseudotumor cerebri in pediatric patients, and have been occasionally also noted with chronic renal failure, heart and renal transplantation. We report a 7-year-old boy who complained of severe headaches and visual impairment 2 years after hemodialysis for renal hypoplasia. Pseudotumor cerebri was suspected and, despite treatment with corticosteroids, acetazolamide, and lumboperitoneal diversion, visual impairment worsened. Bilateral optic nerve sheath decompression (ONSD) was performed without success and the child completely lost his vision within 2 weeks. He was successfully transplanted 2 months later. Two years post transplantation, the blind child has a normal renal function and school performance. Pseudotumor cerebri must be rapidly suspected in a child with renal failure suffering from headaches and papilledema. Visual loss may progress rapidly and ONSD seems to be the best surgical treatment when medical treatment fails. In this patient renal transplantation was well tolerated, with no deterioration in the neurological status over 2 years of follow-up.     

A long-term clinical analysis of the rheumatoid patients treated by a combination of GST and CCA

It has been well known that DMARDs are very effective for rheumatoid arthritis but lose their effect after long term administration. The authors would expect that Lobenzarit disodium (CCA) could slow the reduction of effectiveness of the DMARDs. The aim of this paper is to clarify the effects of Lobenzarit disodium (CCA) for the rheumatoid patients maintained by sodium aurothiomalate and D-penicillamine. The classical and definite rheumatoid patients were divided into two groups. One (group-A) was the rheumatoid patients who were treated in combination with CCA (79 patients). Another (group-B) was rheumatoid patients who were treated by sodium aurothiomalate or D-penicillamine (78 patients). All of them were followed for four years. In group-A, Lansbury index didn't improve in comparison with group-B. However, in the parameters of Lansbury index, improvement of the swelling joints was clearly higher in group-A than in group-B. Furthermore, this effect started in three months after administration of CCA and continued until the end of this study. On the other hand, according to roentogenographic examination utilizing MD's method, density of the metacarpal bones decreased more in group-B than in group-A. The sid-effects were few. They were five cases of gastrointestinal disorders and three cases of renal dysfunction. However, the renal dysfunction seems unlikely to be causally related to CCA. The authors could confirm the certain and expected results of combination therapy with CCA and sodium aurothiomalate and D-penicillamine for the rheumatoid patients.     

The impact of sacral root anatomy on selective electrical stimulation for bladder evacuation

The present study was conducted to examine the clinicopathological features of recurrent IgA nephropathy (IgAN) following renal transplantation. Serial renal biopsies were performed regularly at 0-hour, 1-hour and 2-hours, and 39 episode biopsies were carried out when patients had increased serum creatinine levels and proteinuria. In 49 renal allograft recipients with IgAN, 12 patients were proved to be recurrent IgAN (24.5%). There was a significantly increased five- and ten-year risk of graft loss in the renal allograft recipients with biopsy-proved recurrent IgAN. Graft survival in 49 renal allograft recipients with IgAN was worse (68.8% at 5 years and 40.4% at 10 years) than that in 997 whole transplants (80.7% at 5 years, and 67.7% at 10 years). We found significant differences in the prevalence of HLA-DR4 (66.7%) and BW35 (25%) in the renal allograft recipients with recurrent IgAN when compared with normal healthy subjects. The renal allograft recipients with recurrent IgAN had a high incidence of proteinuria (8/12), hypertension (9/12) and renal dysfunction of less than 50 ml/min (7/12). Mean hemodialysis duration before renal transplantation in recurrent IgAN transplants was 12.5 months, which was shorter than in those without recurrent IgAN. Histopathological studies revealed that renal lesions due to IgAN frequently appeared in the renal allograft recipients with recurrent IgAN. Taken together, these findings suggest that donor-recipient matching may be carefully reconsidered, and recurrent IgAN after renal transplantation must be treated with effective immunosuppressive therapy.     

The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone

To determine the safety and efficacy of viscosupplementation with hylan G-F 20, a cross-linked hyaluronan preparation, used either alone or in combination with continuous non-steroidal anti-inflammatory drug (NSAID) therapy, a randomized, controlled, multicenter clinical trial, assessed by a blinded assessor, was conducted in 102 patients with osteoarthritis (OA) of the knee. All patients were on continuous NSAID therapy for at least 30 days prior to entering the study. Patients were randomized into three parallel groups: (1) NSAID continuation plus three control arthrocenteses at weekly intervals; (2) NSAID discontinuation but with three weekly intra-articular injections of hylan G-F 20; and (3) NSAID continuation plus three injections, one every week, intra-articular injections of hylan G-F 20. Outcome measures of pain and joint function were evaluated by both the patients and an evaluator at baseline and weeks 1, 2, 3, 7 and 12, with a follow-up telephone evaluation at 26 weeks. At 12 weeks all groups showed statistically significant improvements from baseline, but did not differ from each other. A statistical test for the equivalence, the q-statistic, demonstrated that viscosupplementation with hylan G-F 20 was at least as good or better than continuous NSAID therapy for all outcome measurements except activity restriction. At 26 weeks both groups receiving hylan G-F 20 were significantly better than the group receiving NSAIDs alone. A transient local reaction was observed in three patients after hylan G-F 20 injection; only one patient withdrew from the study as a result and all recovered without any sequela. Hylan G-F 20 is a safe and effective treatment for OA of the knee and can be used either as a replacement for or an adjunct to NSAID therapy.     

Evaluation of the renal protective effect of misoprostol in elderly, osteoarthritic patients at risk for nonsteroidal anti-inflammatory drug-induced renal dysfunction

An age greater than 60 and diuretic use have been implicated as risk factors for nonsteroidal anti-inflammatory drug (NSAID)-induced decreases in renal function. Misoprostol, a prostaglandin E1 analog, was studied in nine elderly osteoarthritic patients at risk for NSAID-induced renal dysfunction to determine whether it could prevent NSAID-induced renal dysfunction. Subjects received ibuprofen 2400 mg/day and either misoprostol 800 mcg/day or placebo for 14 days in a randomized, double-blinded, crossover trial. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) studies using inulin and PAH plasma clearance, urinary prostaglandin E2 (PGE2) and protein excretion, and serum electrolytes were obtained at baseline, after the first dose, and on day 7 and 14 of each treatment period. Prostaglandin E2 excretion was significantly reduced after the first dose of ibuprofen and throughout the 14 days in both the misoprostol and placebo treatment groups. No statistically significant differences in GFR, ERPF, protein excretion, serum potassium, or serum sodium were detected between misoprostol and placebo treatment during the 14 days of ibuprofen treatment. However, a subset of two patients who exhibited a decrease of greater than 20% in GFR during placebo treatment, appeared to demonstrate an attenuation of this decline when treated with misoprostol. Effect of time, independent of treatment group, indicated that ERPF was significantly decreased from baseline after the first dose of ibuprofen (P < or = 0.05), whereas GFR was notably diminished from baseline on day 14 only (P < or = 0.05). Misoprostol does not influence GFR and ERPF in unselected subjects purportedly at risk for NSAID-induced renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperdynamic hemodynamics following high-dose interleukin 2-interferon alpha therapy in patients with metastatic renal cell carcinoma. Immunotherapy as a clinical sepsis model?

Human recombinant interleukin 2 (IL-2), alone or in combination with other cytokines, is currently under investigation for the immunotherapy of metastatic tumours. Objective responses of 20-35% have been reported in patients with disseminated melanoma and renal cell carcinoma who received high-dose intravenous IL-2 in combination with interferon-alpha (IFN alpha). However, treatment with IL-2 is complicated by a syndrome of life-threatening adverse reactions such as disseminated vascular leakage, fluid retention, severe hypotension, and (reversible) multiple organ dysfunction (MODS). A systemic inflammatory reaction (SIRS/sepsis sepsis-like haemodynamic pattern has been described in patients after IL-2 bolus application alone. Our purpose was to study the haemodynamic changes in patients treated with high-dose IL-2 administered as a constant infusion and in combination with IFN alpha. PATIENTS AND METHODS: Haemodynamic variables were obtained during therapy courses of 11 patients (aged 48 to 71 years, median 61) with metastatic renal cell carcinoma receiving immunotherapy with IL-2/IFN alpha. Therapy consisted in IFN alpha 10 x 10(10) IU/m2 body surface area (BSA) once daily on days 1-5 i.m. on a regular ward, followed by IL-2 as a constant infusion of 18 x 10(6) IU/m2 BSA on days 6-11 in an intensive care unit (ICU). Haemodynamics were first measured after 5 days of IFN alpha application and transfer to the ICU on day 6, a further 24 h after the beginning of IL-2 infusion (day 7), and the end of the therapy course (days 10 and 11). Mean arterial pressure (MAP) was measured noninvasively using an oscillometric device (Dinamap, Critikon). Mixed-venous oxygen saturation (sv O2) was measured using an CO-oxymeter (OSM 3, Radiometer) and peripheral arterial oxygen saturation (psaO2) was recorded continuously with a pulse oximeter (Oxyshuttle, Critikon). In case of haemodynamic instability, stabilisation had priority over invasive haemodynamic measurements, so that nadir values of blood pressure (BP) did not influence mean MAP and are reported separately. Lactate values and criteria for SIRS were obtained before and during IL-2 infusion. Lactate measurements were performed using an enzymatic essay (Abbot FLx). The mean effect size of the haemodynamic values, SIRS criteria, and lactate concentrations during IL-2 infusion (days 6-11) were calculated, and 95% confidence intervals for the effect sizes are indicated. RESULTS: After their daily i.m. injections of IFN alpha, patients had short episodes of fever and tachycardia without significant drops in BP. A few hours after transfer to the ICU and continuous infusion of IL-2, they developed a syndrome of fever, tachycardia and tachypnoea. The haemodynamic values after 5 days of IFN alpha therapy remained in the normal range, whereas those during IL-2 infusion strongly resembled SIRS and sepsis, with a decrease in MAP (98 to 28 mm Hg) and systemic vascular resistance (SVR, 1477 to 805 dyn.s.cm-5) and an increase in cardiac output (cardiac index 2.8 to 4.3 l.min-1.m-2). MAP often had to be stablilized with colloids during the last 48 h of therapy; 5 patients had nadir values below 60 mm Hg, or 30% below basic values in hypertensive patients. Catecholamine therapy became mandatory in 1 patient and therapy had to be discontinued. Surprisingly, some patients already had elevated plasma lactate concentrations after IFN alpha therapy. During IL-2 infusion mean plasma lactate levels increased from 2.3 to 3.2 mmol.l-1 and all patients had lactate concentrations above 2.0 mmol.l-1 at the end of therapy. During the last 48 to 72 h of IL-2 infusion, patients suffered from MODS with altered mental state (7 patients), oliogoanuria (all patients), cardiac dysrhythmias (4 patients), congestive heart failure (1 patient, which led to a second case of therapy interruption), elevated bilirubin (4 patients), and pulmonary dysfunction. In 9 patients supplementary oxygen was necessary when psaO2 fell below 92     

What's new in pediatric nephrology?]

Advances in pediatric nephrology has been mainly characterized during the last years by a burst of knowledge in the area of genetic renal diseases: 1/almost complete understanding of Alport syndrome related to mutations of COL4A5 or COL4A3/A4 genes of collagene; 2/the mapping and cloning of the nephronophthisis gene which is deleted in 75% of cases; 3/the mapping and cloning of the cystinosis gene coding for a protein of the lysosomal membrane; 4/the mapping and cloning of the Finnish-type congenital nephrotic syndrome gene; 5/the linkage to the SNR 1 gene on chromosome 1 of a large number of familial corticoresistant nephrotic syndromes, and the disclosure of mutations of the WT1 gene in diffuse mesangial sclerosis and in Frazier syndrome. The understanding of Bartter syndrome has been also enlightened by the discovery of mutations in several ionic channels located in the distal tubule. It has been also shown that a corticoresistant nephrotic syndrome or a chronic tubular interstitial nephropathy are possible phenotypes for mitochondrial cytopathies. In the area of therapeutics, recombinant growth hormone was shown to improve statural growth of children with chronic renal failure; in addition, renal transplantation benefits from new immunosuppressants as tacrolimus and mycophenolate mofetil.     

Metabolic encephalopathy as a complication of renal failure: mechanisms and mediators

Among patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may develop symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and progressive intellectual dysfunction. Peripheral neuropathy is also a major cause of disability in uremic subjects. It is believed that aluminum contributes to the pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in patients with renal failure, probably because of actions of parathyroid hormone on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual dysfunction, dialysis dementia, and uremic neuropathy can be made by the characteristic clinical pictures of these syndromes and the exclusion of other causes of nervous system dysfunction.