Josep Bonet

Effect of drastic weight loss after bariatric surgery on renal parameters in extremely obese patients: long-term follow-up.

Obesity is a health problem that is reaching epidemic proportions. Extreme obesity (body mass index [BMI] > or =40 kg/m2) is a type of obesity that usually does not respond to medical treatment, with surgery being the current treatment of choice. Extreme obesity is associated with cardiovascular disease, type 2 diabetes, dyslipidemia, and hypertension. Recently, obesity has been related with high rate of renal lesions, but renal function and renal parameters in extreme obesity scarcely are documented. The objective of this study was to evaluate the effect of weight loss after bariatric surgery (BS) on BP, renal parameters, and renal function in 61 extremely obese (EO) patients after 24 mo of follow-up. A total of 61 EO adults (37 women) were studied prospectively before and 24 mo after surgery. Control subjects were 24 healthy, normal-weight adults (15 women). Anthropometric, BP, and renal parameters were determined. Presurgery weight, BMI, GFR, 24-h proteinuria, and 24-h albuminuria were higher in the EO patients than in control subjects (P < 0.001). All parameters improved at 12 mo after BS. However, during the second year of follow-up, only 24-h albuminuria (P = 0.006) and BMI (P = 0.014) continued to improve. At 24 mo after BS, obesity-related renal alterations considerably improved. This improvement was observed mainly in the first year after surgery, when the majority of weight loss occurred. However, 24-h albuminuria still improves during the second year of follow-up. It is possible that this decrease in 24-h albuminuria is not GFR related but rather is attributable to the persistence of the decrease in BMI and to the improvement of other weight-related metabolic factors.

Disseminated varicella infection in adult renal allograft recipients: role of mycophenolate mofetil

Disseminated varicella zoster virus (VZV) infection is a rare complication after renal transplantation in adults. We report 4 cases diagnosed in our transplant patients. One of which was a primary infection (chicken pox) with multivisceral involvement (hepatitis, pneumonitis, myocarditis, and disseminated intravascular coagulation). The other 3 patients VZV-seropositive before transplantation suffered from disseminated zoster. No immunosuppressive drug was significantly associated with a higher risk of disseminated VZV infection. However, from our experience, we believe that mycophenolate mofetil (MMF), plays a part in the clinical presentation of the disease. Early treatment with high doses of acyclovir is fundamental in infection control. It is essential to perform a pretransplantation serological VZV study on all patients.

Is there a need for changes in renal biopsy criteria in proteinuria in type 2 diabetes

Criteria for renal biopsy in proteinuric type 2 diabetes mellitus (T2DM) patients have been not defined. Usually criteria for renal biopsy in type 1 diabetes mellitus (T1DM) are used (microhaematuria, absence of diabetic retinopathy (DR), uncharacteristic change in renal function or immunological abnormalities). The aim of this study was to reconsider the indications for renal biopsy in T2DM using T1DM criteria, to determine whether they are useful in identifying patients with potentially treatable lesions. We studied 127 proteinuric patients with T2DM. Renal biopsy was performed in 35 who met the criteria for biopsy. Biopsy revealed diabetic glomerulopathy (DG) in 29 (83%) (in three associated with nondiabetic renal disease), immunoglobulin A (IgA) glomerulonephritis in three, focal glomerulosclerosis in one and normal glomeruli in two. DG was diagnosed in 17 (74%) of the patients without DR, in 18 (78%) of the patients with microhaematuria and in 10 (67%) of the patients with microhaematuria and without DR. All patients with DR had DG alone, except three with sudden unexpected changes in renal function. We conclude that DG is the most commonly found renal lesion in T2DM patients with proteinuria biopsied according to T1DM criteria, even in patients with microhaematuria or without retinopathy. Thus, these biopsy criteria are not useful in identifying patients with potentially treatable other renal diseases.

Prevalencia y características del síndrome metabólico en la población hipertensa española

BACKGROUND AND OBJECTIVE: Metabolic syndrome (MS) constitutes a risk factor for the development of both type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the prevalence and clinical characteristics of metabolic syndrome in a sample of the hypertensive population. PATIENTS AND METHOD: Cross-sectional epidemiological study in 19,039 hypertensive patients attended in primary care centres. MS was defined using the National Education Cholesterol Program (NCEP) and the International Diabetes Federation (IDF) criteria. RESULT: The 44.6% of patients presented MS using NCEP criteria. This proportion rose to 61.7% when IDF criteria were applied. Compared with hypertensives without MS, those who fulfilled criteria were significantly (p < 0.0001) older, more frequently women, had higher blood pressure values, a poorer blood pressure control (14.4% vs 27.8%) despite the use of more antihypertensive drugs, and suffered more frequently of cardiovascular disease. Other significant abnormalities included higher serum total cholesterol, uric acid, and a decreased estimated glomerular filtration rate. CONCLUSIONS: MS is present in almost half of an unselected hypertensive population (two thirds using the newest criteria). It is more frequent in women than in men and it is associated with mild abnormalities in renal function. MS patients are more refractory to antihypertensive treatment, even with a higher number of antihypertensive drugs.

Adiponectin and risk of new-onset diabetes mellitus after kidney transplantation.

Background. New-onset diabetes mellitus after transplantation (NODAT) is a severe complication of kidney transplantation (KTx) with negative effects upon patient and graft survival. Several risk factors for NODAT have been described; however, the search for an early predictive marker is ongoing. It has recently been demonstrated that high concentrations of adiponectin (APN), which is an adipocyte-derived peptide with antiinflammatory and insulin-sensitizing properties, protect against future development of type 2 diabetes in healthy individuals. The purpose of this report was to study pretransplant insulin resistance and analyze pretransplant serum leptin and APN levels as independent risk factors for the development of NODAT. Methods. A total of 68 KTx patients were studied [mean age, 48±11 years; 70% males; body mass index (BMI), 25±3 kg/m2]; 31 KTx patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar age, sex, BMI, immunosuppression, and posttransplant time were studied. All patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25% cyclosporine A), and 76% of patients received mycophenolate mofetil. Family history of diabetes mellitus was recorded. Pretransplant homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated from fasting plasma glucose and insulin. Pretransplant serum leptin and APN levels were determined by radioimmunoassay. Results. NODAT patients showed higher pretransplant plasma insulin concentrations [NODAT, 13.4 (11–22.7) &mgr;IU/mL; non-NODAT, 10.05 (7.45–18.4) &mgr;IU/mL; P=0.049], HOMA-IR index [NODAT, 4.18 (2.49–5.75); non-NODAT, 2.63 (1.52–4.68); P=0.043], and lower pretransplant serum APN concentration [NODAT, 8.78 (7.2–11.38) &mgr;g/mL; non-NODAT, 11.4 (8.56–15.27) &mgr;g/mL, P=0.012]. Inverse correlations between APN and BMI (r=−0.33; P=0.014) and APN and HOMA-IR index (r=−0.39; P=0.002) and between APN and NODAT (r=−0.31; P=0.011) were observed. Multiple logistic regression analysis showed the patients with lower pretransplant APN concentrations to be those at greater risk of developing NODAT [Odds Ratio=0.832 (0.71–0.96); P=0.01]. Conclusion. Pretransplant serum APN concentration is an independent predictive factor for NODAT development in kidney-transplanted patients.

Undiagnosed obesity in hypertension: Clinical and therapeutic implications

Objectives. The aim of this study was to determine the prevalence of obesity in patients with hypertension and to evaluate the relationship between obesity, metabolic syndrome (MetS) and blood pressure (BP) control. Materials and methods. We conducted an epidemiological survey in a sample of 19,039 patients with hypertension who consecutively attended a primary healthcare center. Patients were considered to have hypertension if the BP was ⩾140/90 mmHg or ⩾130/80 mmHg in diabetic patients or if they were undergoing pharmacological treatment for hypertension. The obesity was based on body mass index (BMI). Overweight was if the BMI was ⩾25 kg/m2, obese ⩾30 kg/m2 and severe obesity (SO) if BMI was ⩾40 kg/m2. Abdominal obesity (AO) was considered when the waist circumference was greater than 102 cm in men and 88 cm in women. Results. The prevalence of obesity in our hypertensive patients was 51.6% and among these 3.8% had SO. Furthermore, 38.7% were overweight. AO was observed in 66.1% of the whole. Both obesity and AO were significantly more prevalent in women. When evaluating the patients according to categories of BMI, we observed greater levels of BP (from 145.5/84.5 to 149.5/89 mmHg, p<0.0001), worse control over BP (from 29.6% to 15.4%, p<0.0001) and a greater prevalence of MetS (from 20.8% to 66.9%, p<0.0001) as weight increased. Likewise, an increase in both BMI and AO was associated with worse control of BP (obesity, OR = 1.343 (95% confidence interval, CI, 1.251–1.442); AO, OR = 1.292 (95% CI 1.201–1.389). Conclusions. There is a high prevalence in Spain of obesity and AO in patients with hypertension. These conditions are associated with metabolic alterations and worse BP control.

Messenger RNA expression of B7-1 and NPHS1 in urinary sediment could be useful to differentiate between minimal change disease and focal segmental glomerulosclerosis in adult patients

BACKGROUND Podocyte proteins are involved in the pathogenesis of glomerular kidney disease (GKD). However, there is little information on messenger RNA (mRNA) expression patterns of B7-1 and NPHS1 in urinary sediment of patients with GKD. The objective of this study was to analyse the gene expression of B7-1 in urinary sediment and correlate it with the expression of podocyte-specific genes in patients with GKD. METHODS Adult patients with proliferative and non-proliferative GKD, proteinuria and stable renal function, were included. A group of healthy subjects was used to determine normal levels of urinary markers and to obtain reference RNA. Biochemical, clinical and experimental procedures included measurement of creatinine level and total urinary protein, renal biopsy, identification of urinary podocytes, gene expression analysis of B7-1, NPHS1, NPHS2 and SyNPO genes and urinary B7-1 protein analysis by enzyme-linked immunosorbent assay. RESULTS Between June 2006 and November 2009, 69 patients with GKD (median age: 46 ± 15 years, 64% men) and 14 healthy subjects (median age: 34 ± 12 years, 43% men) were included. In both groups, urinary mRNA levels of B7-1 and NPHS1 were significantly higher in patients with GKD compared to healthy subjects (P = 0.050 and P = 0.008, respectively). Regarding GKD subtypes, patients with focal segmental glomerulosclerosis (FSGS), but not patients with minimal change disease (MCD), had a significantly higher mRNA expression of B7-1 and NPHS1 than healthy subjects (P = 0.012 and P = 0.030, respectively). Patients with MCD had a significantly lower NPHS1 mRNA expression than patients with FSGS (P = 0.012). The B7-1:NPHS1 urinary mRNA ratio was significantly higher in patients with MCD compared with patients with FSGS (P = 0.027). CONCLUSION mRNA expression analysis of B7-1 and NPHS1 in urinary sediment may be useful to differentiate between different histologic subtypes of GKD, particularly between MCD and FSGS.

Cinacalcet may reduce arterial stiffness in patients with chronic renal disease and secondary hyperparathyroidism - results of a small-scale, prospective, observational study.

AIMS This study evaluated the impact of cinacalcet on arterial stiffness, determined by pulse wave velocity (PWV), in patients with chronic renal disease and secondary hyperparathyroidism (SHPT). PATIENTS AND METHODS This prospective, observational study included, SHPT patients with chronic renal disease on dialysis undergoing cinacalcet treatment with a follow-up of 12 months. RESULTS 21 patients, 62% males, with a mean age of 51.3 years (± 18.0) were included. Cinacalcet was given for at least a year with a mean daily dose of 35 mg (range 30-60 mg). Aortic PWV significantly decreased after 12 months of cinacalcet treatment (9.35 ± 1.83 m/sg vs. 8.66 ± 1.86 m/sg; p = 0.030). Additionally, there was a notable reduction trend in the left ventricular mass index (166.6 ± 39.4 g/m² vs. 156.1 ± 31.8 g/m²), although it did not achieve statistical significance (p = 0.063). Alkaline phosphatase and PTH were significantly decreased during the study. However, serum calcium, phosphorus and blood pressure remained stable. CONCLUSION The results of this study support the possibility that cinacalcet reduces arterial stiffness of SHPT patients with chronic renal disease after 12 months of treatment. Prospective, randomized clinical trials are needed to confirm these preliminary findings.

Uromodulin and α1-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

Background/Aims: Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. Methods: Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS. Results: The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α1-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80–92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels – focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease. Conclusion: We describe a workflow – urinary peptide profiling coupled with histological findings – that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.

Prevalencia de microalbuminuria en la población general de un área mediterránea española y su asociación con otros factores de riesgo cardiovascular

Fundamento Conocer la prevalencia de la microalbuminuria en la poblacion general de un area mediterranea espanola y su asociacion con otros factores de riesgo cardiovascular. Pacientes Y MeTodo Se estudiaron 399 pacientes consecutivos y se dividieron segun tuviesen una microalbuminuria superior o inferior a 30 mg/24 h en 2 de 3 muestras. Resultados En 37 pacientes se detecto microalbuminuria (9,3% de la poblacion general y 21% de los hipertensos). La microalbuminuria se correlaciono con la edad, el valor de presion sistolica, el indice de masa corporal, el indice cintura-cadera, presion de pulso, el colesterol ligado a lipoproteinas de alta densidad, los trigliceridos, la glucemia y la creatinina serica. La microalbuminuria en los no hipertensos ni diabeticos fue de 12,9 (11,2) mg/dia, en los diabeticos no hipertensos de 14,1 (16,5) mg/dia, en hipertensos no diabeticos de 22,5 (53,5) mg/dia y en los diabeticos e hipertensos de 27,7 (49,1) mg/dia. La presencia de hipertension arterial determino la aparicion de microalbuminuria y el riesgo (OR) de presentar microalbuminuria fue de 2,4 (IC del 95%, 1,1- 5,2), y si se asociaba a sexo varon, de 3,8 (IC del 95%, 1,8-8,1). Conclusiones La prevalencia de la microalbuminuria en esta area mediterranea es baja (9,3%) pero si se asocia a otros factores de riesgo cardiovascular aumenta a un 21%. Los valores de microalbuminuria mas elevados se encuentran en los pacientes hipertensos y varones, se asocie o no diabetes.