Ramón Romero

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.

Renal injury in the extremely obese patients with normal renal function

We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were non-diabetic, non-hypertensive, and were undergoing nephrectomy or donating a kidney. Logistic regression models determined associations between the clinical and biochemical variables and glomerular lesions. Arterial hypertension, sleep apnea syndrome (SAS), and microalbuminuria were prevalent in the obese patients, as was hyperglycemia to a lesser extent. Focal and segmental glomerulosclerosis was present in only five extremely obese (EO) patients but absent in controls. Increased mesangial matrix, podocyte hypertrophy, mesangial cell proliferation, and glomerulomegaly were more frequent in the obese cohort than in the control group. Body mass index was a significant independent risk factor associated with glomerular lesions in all 135 patients and in the 95 EO patients, whereas SAS was associated with glomerulomegaly only in the EO. Our study shows that EO patients who lack overt clinical renal symptoms have a variety of glomerular abnormalities that correlate with body mass.

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.

The effect of cholecalciferol for lowering albuminuria in chronic kidney disease: a prospective controlled study

BACKGROUND Growing evidence indicates that vitamin D receptor activation may have antiproteinuric effects. We aimed to evaluate whether vitamin D supplementation with daily cholecalciferol could reduce albuminuria in proteinuric chronic kidney disease (CKD) patients. METHODS This 6-month prospective, controlled, intervention study enrolled 101 non-dialysis CKD patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666 IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of their vitamin D status, did not receive any cholecalciferol, and were considered as the control group. RESULTS Cholecalciferol administration led to a rise in mean 25(OH)D levels by 53.0 ± 41.6% (P < 0.001). Urinary albumin-to-creatinine ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284 (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol group, and there was no change in the control group. Reduction in a uACR was observed in the absence of significant changes in other factors, which could affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive treatment. Six-month changes in 25(OH)D levels were significantly and inversely associated with that in the uACR (Pearsons R = -0.519; P = 0.036), after adjustment by age, sex, body mass index, BP, glomerular filtration rate and antiproteinuric treatment. The mean PTH decreased by -13.8 ± 20.3% (P = 0.039) only in treated patients, with a mild rise in phosphate and calcium-phosphate product [7.0 ± 14.7% (P = 0.002) and 7.2 ± 15.2% (P = 0.003), respectively]. CONCLUSIONS In addition to improving hyperparathyroidism, vitamin D supplementation with daily cholecalciferol had a beneficial effect in decreasing albuminuria with potential effects on delaying the progression of CKD.

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.

Obesity, inflammation, and kidney disease

Obesity and extreme obesity are associated with a wide range of well known comorbidities (cardiovascular disease, dyslipidemia, hypertension, diabetes mellitus, metabolic syndrome). Recently, the association between obesity and renal involvement has been accepted since several epidemiological and pathological studies support this relationship. However, the physiopathological mechanism of this association is not completely understood. Different mechanisms have been implicated in the production of these renal lesions. Between them, metabolic alterations and inflammatory adipocytokines have been suggested. This paper is a review of the association between inflammatory adipocytokines or metabolic syndrome with renal involvement. We also briefly report our experience in a cohort of extremely obese 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.

A Comparison of Prediction Equations for Estimating Glomerular Filtration Rate in Adult Patients with Chronic Kidney Disease Stages 4–5

Background: The accuracy of prediction equations has not been validated in adult patients with chronic kidney disease (CKD) stages 4–5 in extreme situations of nutritional status and age. Objective and Methods: The significance of nutritional status, calculated with the creatinine production (CP) formula, and age (≤64 years and >64 years) in the application of different prediction equations – modification of diet in renal disease (MDRD), simplified MDRD (sMDRD), Cockcroft-Gault (CG) – and the mean of urea and creatinine clearance (Cr-Ur) compared with the isotopic glomerular filtration rate (GFR) estimation calculated by 51Cr-EDTA was studied in 87 Caucasian adults with CKD stages 4–5 (GFR: 30–8 ml/min/1.73 m2). The Bland-Altman method and Lin’s concordance coefficient (Rc) were used to study accuracy (bias) and precision. Results: The GFR calculated with 51Cr-EDTA in the study group was 22.2 ± 6.9 ml/min/1.73 m2 (range: 8–30). CG and sMDRD were the best prediction equations with bias of –1.1 and –3.8 ml/min/1.73 m2 and Rc of 0.52–0.50. In this situation, the mean Cr-Ur proved the most inaccurate equation compared with the isotopic technique with bias of –5.4 ml/min/1.73 m2 and Rc of 0.32. In the analysis of patients with higher CP (> 0.90; n = 44), CG and sMDRD obtained the best bias of 1.2 and –2.7 ml/min/1.73 m2 and Rc of 0.54–0.53. In patients aged ≤64 (n = 44), these equations obtained a bias of 1.1 and –3.6 ml/min/1.73 m2 and Rc 0.50–0.49. Both in lower CP (≤0.90; n = 43) and older age (>64 years; n = 43), all the equations underestimated the value obtained with isotopic GFR. In these situations, the results obtained with CG had a bias of –2.2 and –3.6 ml/min/1.73 m2 (Rc 0.29–0.56) and with sMDRD –4.0 and –4.1 ml/min/1.73 m2 (Rc 0.39–0.51). In these circumstances, Cr-Ur was the most inaccurate equation, obtaining a bias of –10.1 and –13.2 ml/min/1.73 m2 (Rc 0.14–0.16). Conclusions: In the group with higher CP and age ≤64 years, results of the presented data yielded no evidence for superiority of the MDRD equation over CG formula in patients with advanced renal failure. On the basis of our results, we do not recommend the use of the Cr-Ur adjusted to 1.73 m2 of body surface area, which was the most imprecise equation. Application of all the equations proved inaccurate in lower CP patients with or without advanced age, implying the premature start of substitution renal treatment. In these circumstances, ambulatory GFR determination by isotopic techniques would be indicated.