Progressão da doença renal crônica : experiência ambulatorial em Santarém-Pará Progression of chronic kidney disease : ambulatory experience in Santarém-Pará

Introdução: A doença renal crônica (DRC) é um crescente problema de saúde pública. Ainda assim, há poucos dados sobre DRC no Brasil, principalmente nos seus estágios não dialíticos. Objetivo: Conhecer aspectos demográficos, clínicos e laboratoriais de pacientes com DRC não dialítica e avaliar o impacto dessas variáveis na progressão da doença. Métodos: Estudo de coorte retrospectiva, composta de 65 pacientes adultos com DRC nos estágios 2-4, acompanhados e tratados ambulatorialmente por média de 28,24 ± 13,3 meses. Resultados: A idade média foi de 64,6 ± 12,6 anos. As principais etiologias de DRC foram doença renal diabética (DRD) (47,7%) e nefroesclerose hipertensiva (34,2%). A maioria dos pacientes encontrava-se no estágio 3 da DRC (44,6%) e a minoria alcançou os alvos terapêuticos no controle de suas comorbidades, 40% para pressão arterial e 38,7% para o controle glicêmico. A perda média anual da taxa de filtração glomerular (TFG) foi 3,1 ± 7,3 mL/min/1,73 m2 (mediana 1,4 mL/min/1,73 m2) e 21,5% dos pacientes evoluíram com DRC Progressiva. Pressão arterial diastólica (PAD) ≥ 90 mmHg aumentou 2,7 vezes o risco de evoluir com DRC progressiva (IC 95%; 1,14-6,57; p = 0,0341), assim como pressão arterial sistólica (PAS) ≥ 160 mmHg (RR = 3,64; IC 95%; 1,53-8,65; p = 0,0053) e proteinúria (RR = 4,05; IC 95%; 1,5510,56; p = 0,0031). Foi observada também média de PAS maior (p = 0,0359) e mediana de HDL-c menor (p = 0,0047) nos pacientes com DRC Progressiva. Conclusão: Neste estudo, hipertensão e proteinúria foram fatores de risco para evolução com DRC progressiva. Apesar do difícil controle clínico, a minoria dos pacientes evoluiu com a forma progressiva da DRC. Resumo


IntroductIon
Chronic kidney disease (CKD) has become a significant global public health issue.Its impact is felt in patient quality of life and life expectancy, and significantly affects health care expenditure.Estimates indicate that ten percent of the adult population in the USA has CKD, with incidence rates among the elderly ranging between 38% and 44%. 1,2Very little data is available in Brazil on non-dialysis dependent CKD.However, a review on lab test results of adult Brazilian patients revealed that 2.3% of the subjects had GFR < 45 mL/min/1.73m 2 , the equivalent to an estimated 2.9 million Brazilians with CKD stages 3B and higher. 3Following this trend, the number of patients on renal replacement therapy (RRT) in Brazil grew significantly in the last decade, from 42,000 patients in 2000 to over 92,091 in 2010, or 483 patients per million population (pmp).The figures are lower in Northern Brazil (265) and higher in the Brazilian Southeast (591), with hypertensive nephrosclerosis ranking first among the causes of CKD in patients on RRT, followed by diabetic nephropathy. 4any factors have been correlated with CKD progression: uncontrolled systemic hypertension, proteinuria, use of nephrotoxic drugs, urinary tract obstruction, diabetes mellitus, vesicoureteral reflux, high protein diet, smoking, urinary tract infection, obesity, dyslipidemia, chronic anemia, metabolic acidosis, vitamin D deficiency, hyperphosphatemia, and active baseline disease. 5,6The correction of hyperuricemia has been correlated by some authors with lesser drops in the GFR of patients with predialysis chronic kidney disease. 7,8I: 10.5935/0101-2800.20130017managed during follow-up as per the targets set in the main guidelines and trials.Patients under control had blood pressures < 140/90 mmHg; 13 glycemic control, fast glucose < 130 mg/dL (tolerable); 14 lipid control, 15 HDL-c ≥ 50 mg/dL for women and ≥ 40 mg/dL for men, LDL-c < 100 mg/dL, TGL < 150 mg/ dL; uricemia control, 7 serum uric acid < 7.6 mg/dl.Levels of systemic hypertension were defined as per the categories described by the Brazilian Association of Cardiology (SBC). 16Proteinuria was diagnosed in patients with sustained albuminuria > 300 mg/day without identified reversible cause. 9Patients taking at least one RAAS inhibitor for at least six consecutive months were considered users of this drug class.
The clinical endpoint was progressive CKD as defined by the NICE 13 (annual decrease in GFR > 5 mL/min/1.73m 2 or decrease greater than 10 mL/ min/1.73m 2 in five years) after at least one year of follow-up.

results
The mean age of the 65 included patients was 64.6 (± 12.6) years.Sixty-seven percent of the enrolled individuals were 60 and older, and 59% were females.The main etiologies for CKD were diabetic nephropathy (47.7%), hypertensive nephrosclerosis (34.2%), and adult polycystic kidney disease (7.6%).Most patients (44.6%) had stage 3 disease at the time of hospitalization -18.5% on IIIA and 26.1% on IIIB -and had a mean GFR of 40.8 ± 17.8 mL/min/1.73m 2 .Eighty-three percent of the patients had hypertension.Only 40% of them had mean blood pressure levels under control.Uncontrolled patients had very high levels of systolic blood pressure (161.6 ± 17.9 Within the last decades the management of factors connected to CKD progression has been the cornerstone of conservative therapeutic approaches for predialysis CKD patients. 6,9In the realm of drug therapies, renin-angiotensin-aldosterone system (RAAS) inhibitors have been used effectively to hinder the progression of CKD. 10,11his study aimed to find the demographic, clinical, and lab test characteristics of patients with non-dialysis dependent CKD and the impact of these variables in disease progression.

Methods
Sixty-five patients submitted conservative treatment were enrolled in the study.They were 18 years and older and had CKD stages 2, 3A, 3B, and 4. The members of this retrospective cohort were followed for over a year, between June of 2006 and June of 2012 (mean of 28.24 ± 13.3 months) at the Nephrology Ward of the Low Amazon Teaching and Health Care Unit (UEASBA) maintained by the Pará State University (UEPA) in the municipality of Santarém.The service is run by a multidisciplinary team that provides patients with nutritional guidance, psychological advice, physical therapy, nursing care and the aid of social workers and physicians from other medical specialties when needed.As a routine, CKD patients on stage 2 are seen every four months by a nephrologist; stage 3 individuals are seen every quarter; and stage 4 patients are seen every two months.
All patients seen at the ward are tested for creatinine, glucose, and serum uric acid levels, in addition to undergoing simple urine testing and estimation of the glomerular filtration rate (GFR) as per the formula proposed by Cockcroft & Gault. 12Glycated hemoglobin (for diabetic patients), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and 24-hour urinary protein tests are run routinely and were considered in this study.The clinical variables considered were cause of CKD, use of renin-angiotensin-aldosterone system (RAAS) inhibitors [angiotensin-converting-enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARBs)] and blood pressure.Age and gender were included as demographic variables.
Mean values were calculated for lab test results and blood pressure levels, and subjects were divided based on whether or not these parameters were controlled and if the comorbidities they had were adequately Univariate analysis revealed that mean systolic blood pressures were significantly higher in patients with progressive CKD (p = 0.0359).Median HDL-c levels were significantly lower in progressive CKD patients (p = 0.0047), as seen in Table 2.

dIscussIon
A significant portion of the studied population was made up of elderly patients (64.6%), and the sample's mean age was 64.6 ± 12.6 years.The high number of comorbidities per subject (3.11 ± 0.93) was consistent with the literature, 17,18 in addition to being expected in cases of CKD.The predominance of diabetic nephropathy in the etiology of CKD seen in this study was not reported in other Brazilian studies, but was consistent with the findings described in the CKD population in the USA 17 and agreed with the etiologies found in RRT patients treated in Santarém. 19ost of the patients in the sample (44.6%) were referred to a nephrologist when they had stage 3 CKD.This is a positive finding, as other studies carried out in Brazil indicated that most patients on RRT were referred to nephrology services only when they had stage 4 disease. 18,20,21he low rates of controlled systemic hypertension (40%) and glucose levels (38.7%) are preoccupying, once both are part of the goals of CKD treatment. 6tista et al. reported similar rates: 34.4% and 65% for controlled BP and glucose levels, respectively. 21n the other hand, a significant number of patients was on RAAS inhibitors (77%).Another Brazilian retrospective study reported similar findings. 18Batista et al. and Kausz et al. assessed the fact that only 65% of the patients enrolled in the study were on RAAS inhibitors as a negative finding. 21,22These studies used different methods and cutoff points, but their authors showed how difficult it is to conservatively manage patients with chronic kidney disease and reach treatment goals.
Dichotomized analysis revealed that proteinuria, high levels of systolic blood pressure, and diastolic hypertension were risk factors for unfavorable renal outcome (progressive CKD) and worse disease evolution. 6he correlation observed in this study between proteinuria and renal disease progression has been reported by other authors. 23,246][27][28] Pereira et al. reported correlations between higher levels of proteinuria at the time of admission in an outpatient service for CKD treatment with death and RRT. 18any authors have described the benefits of blood pressure management as a protective factor against CKD progression. 29,30Nonetheless, targets vary between the main guidelines and the most recent studies.Although the World Health Organization (WHO) 31 and the Kidney/Disease Outcomes Quality Initiative (K/DOQI) 32 recommend blood pressure levels ≤ 130/85 mmHg, a recent meta-analysis 33 concluded that no additional benefit was produced when BP was kept at these levels when compared to 140 x 90 mmHg and under, with the exception of patients with proteinuria between 300 and 1,000 mg/24h, as also supported by the NICE. 13In this study, patients with systolic BP equal to or greater than 160 mmHg (SBC stage ≥ 2) 16 and individuals with systolic hypertension were at higher risk of developing progressive CKD.Additionally, patients with unfavorable CKD progression had significantly higher mean systolic BP levels than patients evolving favorably.
Multiple studies have looked into the high prevalence of dyslipidemia in CKD patients and the correlations between cholesterol and progression of renal dysfunction.In this study, significantly higher median levels of HDL-c were seen in patients with favorable CKD progression.However, controversy looms over the benefits of statin-based lipid control in limiting the progression of CKD.Most studies on the topic disagree on the main benefits offered by these drugs to such end.If, on the one hand, the 4S trial 34 showed reduced rates of CKD progression with statins, the ALLHAT 35 study did not report the same results.This disagreement does not disavow the established correlation between the use of statins and lower cardiovascular morbidity and mortality rates. 36he mean annual decrease in GFR was 3.1 ± 7.3 mL/min/1.73m 2 with a median of 1.4 mL/ min/1.73m 2 .Despite the difficulties achieving clinical and workup control over the variables classically correlated with CKD progression, these levels were lower than the thresholds established in the CKD guidelines (NICE). 16Additionally, only 21.5% of the patients developed progressive CKD.Pereira et al.
carried out a retrospective study with patients seen at an integrated predialysis CKD care center in Brazil and found lower levels of decreased renal function (0.6 ± 2.5 mL/min/1.73m 2 ). 22conclusIon Diabetic nephropathy was the main etiology of CKD in the studied population.Diastolic hypertension, high levels of systolic blood pressure, and proteinuria were risk factors for decreased renal function.Higher systolic blood pressure levels and lower levels of HDL-c were observed in patients with progressive CKD.The clinical and laboratory workup variables that affect the progression of renal disease are not easily controlled.Nonetheless, most patients did not develop progressive CKD.
This study was approved by the Research Ethics Committee of the Pará State University Campus XII -UEPA (permit nº 40/2012).