Silver jubilee: 25 years of the first demonstration of the direct effect of phosphate on the parathyroid cell.

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43-), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43- in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43- on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43- overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role.

Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long-Term Renal Function.

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium- and long-term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68-positive cells in DD kidneys, which correlated negatively with long-term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α-smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium- and long-term renal function in DDs. Multivariate analysis point to transforming growth factor-ß1 as the best predictor of long-term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor-ß1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.

Monocyte implication in renal allograft dysfunction.

Macrophages are involved in the development and progression of kidney fibrosis. The aim of this study was to analyse the phenotype of circulating monocytes and their ability to predict kidney allograft dysfunction in living kidney transplant recipients. Whole blood samples from 25 kidney recipients and 17 donors were collected at five time-points. Monocyte phenotype was analysed by flow cytometry, and interleukin (IL)-10 and soluble CD163 by enzyme-linked immunosorbent assay. One week after transplantation, surface CD163 and IL-10 levels increased significantly from baseline [2·99 ± 1·38 mean fluorescence intensity (MFI) to 5·18 ± 2·42 MFI for CD163; 4·5 ± 1·46 pg/ml to 6·7 ± 2·5 pg/ml for IL-10]. This CD163 increase correlated with 4-month creatinine levels (r = 0·4394, P = 0·04). However, soluble CD163 decreased significantly from baseline at 1 week (797·11 ± 340·45 ng/ml to 576·50 ± 293·60 ng/ml). CD14(+) CD16(-) monocytes increased at 4 months and correlated positively with creatinine levels at 12 and 24 months (r = 0·6348, P = 0·002 and r = 0·467, P = 0·028, respectively) and negatively with Modification of Diet in Renal Disease (MDRD) at 12 months (r = 0·6056, P = 0·003). At 4 months, IL-10 decreased significantly (P = 0·008) and correlated positively with creatinine at 2 years (r = 0·68, P = 0·010) and with CD14(+) CD16(-) monocytes at 4 months (r = 0·732, P = 0·004). At 24 h, levels of human leucocyte antigen D-related declined from 12·12 ± 5·99 to 5·21 ± 3·84 and CD86 expression decreased from 2·76 ± 1·08 to 1·87 ± 0·95. Both markers recovered progressively until 12 months, when they decreased again. These results indicate that monitoring monocytes could be a promising new prognostic tool of graft dysfunction in renal transplant patients.

[Prophylactic and pre-emptive therapy for cytomegalovirus infection in kidney transplant patients using oral valganciclovir]. / Tratamiento profiláctico y anticipado de la infección por citomegalovirus en pacientes trasplantados renales mediante valganciclovir oral.

UNLABELLED: Prophylactic and pre-emptive therapy with oral valganciclovir for cytomegalovirus infection in renal transplant recipients. BACKGROUND: Cytomegalovirus infection is a very important health problem in solid organ transplant recipients (SOT). Once-daily valganciclovir has been shown to be as clinically effective and well tolerated as oral ganciclovir tid in the prevention of CMV infection in high risk SOT recipients. METHODS: The aim of the present study was to evaluate the incidence and severity of CMV disease in 150 renal transplant recipients that received either prophylactic [high risk group (HR), N = 66] or pre-emptive [low risk group (LR), N = 84] therapy with oral valganciclovir (900 mg/day vo) for three months according to their basal risk. Patients were monitored for signs and symptoms of CMV disease and CMV plasma viral load was assessed weekly. RESULTS: A total of 31 patients (47%) of the HR and 26 patients (31%) of the LR presented a positive CMV PCR result. Twelve patients (14.3%) in the LR that had a high viral load (CMV PCR > 1,000 copies/mL) but remained asymptomatic received pre-emptive therapy. Four patients (4.7%) in the LR, after an average time of 35 days after transplant and two patients (4.5%) in the HR, after prophylactic treatment was completed, developed CMV disease. The disease was mild-moderate in most of the cases. Those patients that developed CMV disease responded to treatment with iv ganciclovir for 14 days followed by treatment with oral valganciclovir for up to three months. CONCLUSION: Prophylactic treatment with oral valganciclovir for CMV prevention is only required in high risk solid organ transplant recipients.

Hemiparesia secundaria a hiponatremia severa de origen mixto / Hemiparesis secondary to hyponatremia

La hiponatremia es un trastorno electrolítico frecuente y su etiología es muy variada. En el período postoperatorio su aparición no es rara. Las causas más frecuentes en este contexto son el dolor, la sueroterapia hipotónica y en ocasiones el uso de diuréticos. Presentamos un caso de hiponatremia aguda severa con clinica neurológica en el postoperatorio de una nefroureterectomía derecha

Hyponatremia is a frequent electrolytic disorder of quite diverse aetiologies. It is not rare to find it during tbe postoperative period In this context its most frequent causes are pain, hypotonic serum therapy and, occasionally, the use of diuretics. We describe herein a case of severe acute hyponatremia with neurologic manifestations during tbe postoperative period after a right nephroureterectomy

[Steroid-responsive nephrotic syndrome in IgA nephropathy]. / Síndrome nefrótico corticosensible en la enfermedad de Berger.

A 46-year-old male, smoker of half a packet a day and an alcohol intake of 80 grams a day, with an unremarkable medical history, was referred to our service in the year 1988 for a study of nephrotic syndrome. He presented normal renal function, without either microhematuria nor hypertension. In blood analysis an albuminemia of 10 g/l and proteinuria of 22 g/d was observed. A first renal biopsy was carried out which indicated minimal change disease. Steroid treatment was started, as a result the nephrotic syndrome disappeared and the blood analysis normalized. Later he had 4 new outbreaks, all of them steroid-responsive. In 1992 a second renal biopsy was performed after the fourth outbreak and the presence of mild renal failure, that this time indicated a IgA nephropathy. Steroid treatment was tried again, and this time cyclophosphamide was added to try to reduce steroid doses. This result in normalization of renal function and decrease of proteinuria to 2 g/d. The patient remained stable until 1996 when the fifth outbreak occurred, again with mild renal failure and proteinuria in nephrotic range. Therefore a third renal biopsy was performed, that confirmed the presence of IgA nephropathy, but now with signs of histological progression of the disease. Following this, he presented five outbreaks in 3 years, all of them steroid-responsive, with decrease of proteinuria although without renal function normalization. In the year 2000, at his tenth outbreak of nephrotic syndrome it was decided to add cyclosporine to the steroid treatment, achieving the stability of the patient, without further outbreaks until now, with proteinuria of 1.6 g/d and C. creat. 59 ml/min.

[Influence of chronic renal failure and of its treatment on serum erythropoietin]. / Influencia de la insuficiencia renal crónica y de su tratamiento en la eritropoyetina sérica.

BACKGROUND: In order to know the influence of dialysis treatment in erythropoietin production, serum erythropoietin (Ep) has been studied in patients with anemia due to chronic renal failure (CRF). METHODS: Thirty six of them in hemodialysis (HD), 10 in continuous ambulatory peritoneal dialysis (CAPD) and 18 in predialysis stage (PD) and their results were compared to two control groups, including 72 healthy controls (HC) and the second one 89 iron deficiency anemia patients (ID). RESULTS: Patients had lower Hb and Ep levels than the other groups. Although Ep was higher in CAPD and PD. Ep levels were similar to HC values, and lower than ID levels. It could be demonstrated any correlation between Hb and Ep in CRF patients, however a negative exponential correlation was demonstrated in ID patients between Hb and Ep (r = -0.83; p less than 0.00001). In summary, Ep is higher in CAPD and in PD than in HD, but the levels are lower than they should be expected. CONCLUSIONS: These data confirm an Ep production failure in most of IRC patients and it seems likely that Ep treatment could be effective to treat the anemia of CRF.

Plasma and urinary heparin cofactor II levels in patients with nephrotic syndrome.

Heparin cofactor II (HC II) levels were measured by electroimmunoassay in plasmas and urines from 68 patients with nephrotic syndrome. In addition, antithrombin III (AT III) and protein C (PC) activities and antigens were measured also in the same group of patients. Seven of these patients had histories of thrombosis. Plasma HC II levels (mean +/- SD 105 +/- 43) were not different from levels in healthy subjects (94 +/- 17). Only 5 patients had low plasma levels of HC II. None of the patients with thrombosis had low HC II levels. Even though measurable amounts of HC II were found in 25 urines from 50 patients. There was a relationship in the urinary excretion between HC II and AT III and their urinary clearances were quite similar. However, no correlation was found between plasma HC II and AT III levels, and levels of AT III activity and antigen were significantly lower than in healthy subjects. Three patients with histories of thrombosis had low AT III levels. Most patients (including those with thrombosis histories) had high plasma PC levels and increased urinary loss. It is suggested that HC II does not play an important role in the pathogenesis of thrombosis in nephrotic syndrome.

Renal transplantation during pregnancy--a case report.

A case of renal transplantation during the 12th week of pregnancy is presented. An episode of rejection 6 days after surgery was treated satisfactorily. At the 18th week, the patient showed a mild hypertension which was treated by hidralazine. At the 30th week a fetal pyelouretheral stenosis with celiciar dilatation was diagnosed and the mother had another rejection episode. At the 33rd week a cesarean section was performed after a pathological NST. Neonatal and maternal developmental courses were good.

The isolated C3 in the 'vascular pole' in patients with primary haematuria.

Among sixty-four patients with primary haematuria, immunofluorescence methods revealed seven cases (11%) with isolated C3 deposits in the 'vascular pole'. Serum complement were normal and the follow-up after 20-41 months indicate a benign course. In patients with C3 deposits in the 'vascular pole' light microscopy was normal. We never observed C3 deposits in specimens of normal kidney which were processed by the same methods using mono-specific antisera confirmed by immunoelectrophoresis. This entity defined by immunofluorescence methods, can be called 'vascular pole disease'.