Familial nephropathy associated with hyperuricemia in Spain: our experience with 3 families harbouring a UMOD mutation.

Since 1993 we have studied 5 Spanish families with familial nephropathy associated with hyperuricemia (FJHN). Among these families, 24 patients have been identified. All patients had some combination of hyperuricemia, gout, renal insufficiency, arterial hypertension, and reduced kidney size. The clinical presentation in the different families and in the members of the same family was heterogeneous. Allopurinol treatment did not appear to influence renal disease. From a clinical perspective, this syndrome is a distinctive interstitial nephropathy, inherited as an autosomal dominant trait, that progresses to renal failure and is not halted nor prevented by allopurinol therapy. In 2003, genetic linkage analysis in 3 of the 5 families showed linkage of FJHN to 16p 11.2. One family was not analyzed and one family did not show linkage to this region confirming the genetic heterogeneity of this syndrome. A mutation in UMOD gene was found in these 3 families as the cause of the FJHN. The mutations cluster in exon 4 and exon 5 and were point mutation that results in an amino acid change in the uromodulin or Tamm Horsfall protein. This fact allowed in 2004, the presymptomatic genetic diagnosis of an 8-years-old boy belonging to one of these 3 Spanish families. We conclude that in families with a history of renal failure and/or gout in which FJHN is suspected, UMOD mutation screening may enable a definite diagnosis. When a mutation is found, family members can be tested for a UMOD mutation and pre-symptomatic diagnosis may allow counseling to prevent or halt the progression to renal insufficiency.

[Preclinical diagnosis of the familial nephropathy associated to hyperuricemia]. / Diagnóstico preclínico de la nefropatía familiar asociada a hiperuricemia.

We describe one patient with the pre-symptomatic diagnosis of the disease named afamilial nephropathy associated to hyperuricemia)) (OMIM 162000; FJHN). This is a hereditary disease, autosomic dominant, characterized by its progression to renal insufficiency. Several mutations in the gene that codifies uromodulin or Tannn-Horsfall protein (UMOD) have been identified in some families. The clinical presentation is heterogeneous. In some cases the disease appears as juvenile hyperuricemia due to a diminished renal urate excretion, with or without gout, but in some other cases the first manifestation is renal insuffciency. The study of the UMOD gene shows that patient is heterozygous for the mutation C869 --> A, which results in C255Y change, and enabled to establish the diagnosis of FJHN. This patient shows the possibility to identify the genetic alteration associated to FJHN in early stages. This fact implies a clinical follow-up and eventual treatment to reduce the inexorable progression to renal insuffciency.

Recombinant human growth hormone therapy in malnourished dialysis patients: a randomized controlled study.

Recombinant human growth hormone (rhGH; Saizen, Serono, Spain) has been recently used as an anabolic agent in several catabolic states, including malnourished chronic dialysis patients. However, up-to-date, comparative studies with control groups of dialysis patients have not been reported. The aim of the present study was to assess the effects of rhGH on nutritional status in a group of malnourished adult chronic dialysis patients undergoing both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). The patients were randomly assigned to the control group (nine patients; 6 women, 3 men; mean age, 58.3 +/- 5.6 years; seven undergoing CAPD, two undergoing HD) or the rhGH group (eight patients; three women, five men; mean age, 63.9 +/- 3.1 years; four undergoing CAPD, four undergoing HD). Both groups were similar at baseline. All patients were given dietary prescriptions (35 kcal/kg/d and 1 g protein/kg ideal body weight/d) during 4 weeks. In the rhGH group, rhGH was administered at 0.2 IU/kg/d subcutaneously (SC) during this period. Anthropometric and analytic parameters were assessed before (0 weeks) therapy and at 2 and 4 weeks after starting therapy. The rhGH group showed an increase of 1.238 kg in body weight from 64.3 +/- 4.3 (mean +/- standard error of the mean [SEM]) to 65.6 +/- 4.9 kg (P < 0.05). Serum insulin-like growth factor type 1 (IGF-1) concentrations increased from 216.6 +/- 42.5 to 581.2 +/- 171.5 ng/mL (4 weeks; P < 0.01) and transferrin levels increased from 271.2 +/- 16.3 to 314.5 +/- 21.2 mg/dL (4 weeks; P < 0.05). A significant reduction in blood urea nitrogen (BUN) level was observed (62.1 +/- 1.8 v 46.8 +/- 3.8 mg/dL; 4 weeks; P < 0.05). Mean daily protein intake, determined by individual dietary survey, at 0 and 4 weeks, remained constant in both groups. In conclusion, weight gain and IGF-1 and transferrin level increases and BUN level decreases, despite the constant oral intake, suggest that short-term rhGH administration is associated with an anabolic reaction in malnourished dialysis patients.

Renal artery thrombosis occurring in an adult with the idiopathic nephrotic syndrome: results of local treatment with streptokinase.

A 55 year old male with the idiopathic nephrotic syndrome (minimal glomerular lesions by light microscopy and negative immunofluorescent stainings) presented righ renal artery thrombosis as evidenced by clinical and arteriographic findings. Local Streptokinase infusion by means of a renal artery catheter resulted in revascularization of the arterial tree, although recovery of renal function was only partial.

Peritoneal vascular reserve characterization through nitroprusside-induced modification of peritoneal mass transfer coefficients.

The transport of solutes across the peritoneum may be increased by the topical administration of nitroprusside; the effects of the drug seem to be due to an increase in the number of perfused capillaries and/or in their permeability. We have compared the peritoneal mass transfer coefficients (MTC) for urea, creatinine and parathormone (PTH) under basal conditions and after administration of nitroprusside (4.5 mg/l dialysate) in 15 patients under CAPD therapy. The mean increments of the MTC were 48.8% for urea, 77.5% for creatinine and 323% for PTH. The relative MTC increments for the three molecules (taken in pairs) were: MTCPTH/urea' 2.53 times (mean), MTCPTH/creatinine' 1.7 times, and MTCcreatinine/urea' 0.73-times, with very variable ranges. The overall mean increment (OMI) for all three ratios ranged from -1.25 and +6 times. In six patients, some of the relative increments (and in three of them the OMI) were negative but the epidemiological features of these patients revealed no clear data. The OMI shows a direct correlation with the body surface area and an inverse correlation with the the duration of CAPD and ESRD and with the number of peritonitis episodes, albeit without statistical significance. We conclude that the peritoneal vascular reserve has individual characteristics, and that perhaps the OMI or some other similar index might serve to quantify and characterise it, if our findings are confirmed.

[Recurrence and spontaneous remission of nephrotic syndrome in secondary renal amyloidosis]. / Recurrencia y remisión espontánea de síndrome nefrótico en amiloidosis renal secundaria.

Secondary systemic amyloidosis (AA) occurs in association with chronic inflammatory disorders and chronic infections. Regression can occur after therapeutically induced remission of the underlying disease; spontaneous remissions has been reported infrequently. We report a 61 year-old woman, with antecedent pulmonary tuberculosis, who developed a nephrotic syndrome at the time of a respiratory infection. Renal biopsy showed secondary amyloidosis. Remission in the nephrotic syndrome appeared spontaneous, but it recurred in the course of pneumonia, and had a second spontaneous remission a maintained at present.

[Simultaneous presence of antibodies against the glomerular basement membrane and anti-myeloperoxidase antibodies in 2 patients with rapidly progressive glomerulonephritis]. / Presencia simultánea de anticuerpos anti-membrana basal glomerular y anticuerpos anti-mieloperoxidasa en dos pacientes con glomerulonefritis rápidamente progresiva.

We report two patients with rapidly progressive glomerulonephritis without alveolar hemorrhage. Renal biopsy showed extracapillary glomerulonephritis with linear deposits of immunoglobulin G. Serologically anti-glomerular basement membrane antibodies (Ac AMBG) and ANCA anti-myeloperoxidase were present. All patients were treated with steroids, cyclophosphamide and plasma exchange. One patient needed dialysis, and other one died from a renal biopsy complication. We discuss the epidemiologic, pathogenic and prognostic aspects of this association.

[Idiopathic membranous nephropathy in an elderly patient with type 2 diabetes mellitus]. / Nefropatía membranosa idiopática en paciente de edad avanzada con diabetes mellitus tipo 2.

We report an 85 years-old patient with type 2 diabetes mellitus and both clinical and biochemical nephrotic syndrome. The renal biopsy showed membranous nephropathy at stage I-II. There was no evidence of malignancy. The patient was treated with steroids, and two months later the proteinuria had not improved. The objects under discussion are the factors that should lead to suspect the existence of glomerulonephritis, other than diabetic glomerulosclerosis, suggesting the need for kidney biopsy. We also focus on the prognostic and therapeutic relevance, as well as on the common pathogenic aspects.

[Familial Henoch-Schönlein purpura manifested with lung hemorrhage]. / Púrpura de Schönlein-Henoch de carácter familiar exteriorizada como hemorragia pulmonar.

Henoch-Schönlein purpura (HSP) is a necrotizing vasculitis affecting small vessels characterized by nontrombocytopenic purpura. The most characteristic clinical manifestations are purpura, arthritis, abdominal pain, abdominal bleeding and nephritis. Lung hemorrhage is a rare symptom associated with the HSP. Although the subclinical alterations of pulmonary function are frequent in patients with PSH without clinical lung manifestations, the presence of lung hemorrhage is an unusual symptom. We report a case of a patient with hemoptysis and HSP previously asymptomatic.

[Progressive systemic sclerosis associated with anti-myeloperoxidase ANCA vasculitis with renal and cutaneous involvement]. / Esclerosis sistémica progresiva asociada a vasculitis ANCA anti-mieloperoxidasa con afectación renal y cutánea.

Sclerodema renal crisis is the usual form of presentation of renal disease in systemic sclerosis. We report a woman who at age 63 was given a diagnosis of scleroderma with Raynaud's phenomenon and cutaneous, oesophageal and lung involvement but no evidence of renal disease and no treatment with D-penicillamine. Two years later she developed progressive renal failure, nephrotic range proteinuria, haematuria and the presence of serum MPO-ANCA; she was normotensive. Renal biopsy revealed extracapillary and necrotizing glomerulonephritis and skin biopsy showed leucocytoclastic vasculitis. This clinical picture was compatible with necrotizing vasculitis of the microscopic polyarterits type. After treatment with pulse steroids followed by oral steroids and monthly intravenous cyclophosphamide her renal function stabilised and the serum MPO-ANCA disappeared.

[Prevalence of genetic prothrombotic factors (factor V Leiden and II20210 prothrombin mutation) in glomerular nephropathies with or without thrombosis]. / Prevalencia de factores protrombóticos de base genética (factor V Leiden y mutación II20210 de la protrombina) en nefropatías glomerulares con o sin trombosis.

The presence of genetic prothrombotic factors (factor V Leiden and the prothrombin II20210 mutation) was investigated in 38 patients with glomerulonephritis with or without a history of thrombotic events and/or nephrotic syndrome. We found an increased prevalence (36%) of heterozygous factor V Leiden in those patients with a history of thrombotic events. This is ten times the prevalence in the normal Spanish population. Carrier status for this mutation may be a determining factor in the development of thrombotic events along with the acquired disorders of coagulation to which these patients are prone. We found only one patient who was a carrier of the G-A II20210 mutation of the prothrombin gene; this patient had no history of venous thrombosis or embolism. Our findings suggest the need to measure activated protein C resistance and to look for the most frequent genotype causing it, Factor V Leiden, in patients with glomerulonephritis to identify those at risk who may benefit from prophylaxis against thrombosis.

[Carbon tetrachloride poisoning: a report of 3 cases]. / Intoxicación por tetracloruro de carbono: presentación de tres casos.

Carbon tetrachloride is a toxic solvent easily obtained in our country. 3 cases of poisoning by accidental inhalation at place of work. The main clinical manifestations were acute renal failure and toxic hepatopathy. All patients, had a good evolution with dialysis therapy after a few weeks. We comment on some possible additional therapies to be used in treating patients with severe poisoning due to carbon tetrachloride.

Prevalence and clinical characteristics of HIV type 1-infected patients receiving dialysis in Spain: results of a Spanish survey in 2006: GESIDA 48/05 study.

End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

Glomerular nephropathy associated with chronic Q fever.

Of three patients with Coxiella burnetii endocarditis, two developed focal segmental proliferative glomerulonephritis (GN), and the third developed diffuse intracapillary proliferative glomerulonephritis. In one case, a good therapeutic response was followed by partial remission of the renal alterations, but 10 months later there were clinical and histological signs of active glomerular nephropathy, suggesting that the antigenic stimulus persisted. In another case, poor evolution of the infection was accompanied by clinically and histologically aggressive glomerular nephropathy, and advanced renal failure. The third patient, who had diffuse proliferative glomerulonephritis, underwent renal biopsy earlier than the other two cases, and the behavior of the nephropathy has not been aggressive to date. Immunohistopathologic study revealed a diffuse granular deposit of IgM and C3 in all three cases; the first two also presented a discrete linear IgG deposit in the capillary loops. Attempts to identify C burnetii antigen at the glomerular level by immunohistologic techniques failed in two patients. The literature on the association of chronic Q fever with glomerulonephritis is briefly reviewed.