| Abstract|| |
Despite the frequency of sickle cell disease (SCD) in the West African population, the renal changes and outcome associated with it have been poorly characterized. We retrospectively studied 22 renal patients; 19 heterozygous sickle cell trait (AS) and three homozygous (SS) evaluated between 1996-2002. The mean age was 43 years (range from 19-69 years). The observed nephropathies included chronic glomerulonephritis (CGN) in eight (36.3%) cases, advanced chronic renal failure (CRF) in seven (31.8%), chronic tubulointerstitial nephropathy (CTIN) in four cases (18.1%), post-infectious acute glomerulonephritis (AGN) in two(9.1%) cases and pregnancy related nephropathy in one (4.5%) case. Renal biopsy was performed in five (22.7%) patients (three AS and two SS patients); the findings included membranoproliferative glomerulonephritis (MPGN), CTIN, focal and segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis. We conclude that there are various renal abnormalities associated with SCD and optimal management needs early diagnosis and multidisciplinary follow-up.
Keywords: Sickle cell disease, Nephropathies, Chronic renal failure.
|How to cite this article:|
Niang A, Diouf B, Ndiaye/Sene FS, Fall S, Moreira/Diop T. Sickle Cell Disease and the Kidney. Saudi J Kidney Dis Transpl 2004;15:180-4
|How to cite this URL:|
Niang A, Diouf B, Ndiaye/Sene FS, Fall S, Moreira/Diop T. Sickle Cell Disease and the Kidney. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2020 Jun 4];15:180-4. Available from: http://www.sjkdt.org/text.asp?2004/15/2/180/32904
| Introduction|| |
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy that involves a qualitative anomaly of hemoglobin due to substitution of valine for the glutamic acid in the sixth position of (3-globin gene on chromosome 11. The severity of the disease is proportional to the quantity of hemoglobin S (Hb S) in the red cells; sickle cell trait (Hb S < 50%) and homozygous SCD (Hb S > 75 %). In SCD, the abnormal Hb S loses its rheological characteristics and is responsible of the various systemic manifestations including those of the kidney.
Our objective in this report is to analyze the presentation, therapy and outcome of the renal patients with SCD in our region.
| Patients and Methods|| |
We retrospectively studied the clinicobiological, therapy and outcome of 22 renal patients with SCD; 19 heterozygous sickle cell trait (AS) and three homozygous (SS) evaluated at the medical clinic 1 of Le Dantec University Medical School, Dakar, Senegal between 1996-2002.
Post-infectious acute glomerulonephritis (AGN) was defined by the presence of infectious syndrome, oedema, high blood pressure (HBP), moderate proteinuria (<3g/24h) with or without hematuria and with or without renal insufficiency. The histological findings should include endocapillary cellular proliferation associated with neutrophil and deposits of C3.
Chronic glomerulonephritis (CGN) was defined by an active proteinuria or the nephrotic syndrome (NS) with edema, HBP, proteinuria, hematuria with or without renal insufficiency. The histological findings should include glomerular lesions that may be associated with fibrosis.
Chronic tubulointerstitial nephropathy (CTIN) was defined as polyuria with polydipsia, normal or elevated arterial pressure without edema and the histological finding of interstitial fibrosis and tubular atrophy.
| Results|| |
The mean age of the patients was 43 years (range of 15-69 years); 57% of the patients were women. The renal abnormalities found in our study patients included chronic glomerulonephritis (CGN) in eight (36.3%) cases, advanced chronic renal failure (CRF) in seven (31.8%), chronic tubulointerstitial nephropathy (CTIN) in four cases (18.1%), post-infectious acute glomerulonephritis (AGN) in two (9.1%) cases and pregnancy related nephropathy in one (4.5%)case.
All the patients with CRF had SS disease with a mean glomerular filtration rate (GFR) of 21 ml/min at presentation. The patients with CTIN had SS disease and presented with HBP, a moderate proteinuria, and renal insufficiency and with interstitial fibrosis and tubular atrophy.
One of the two patients who presented with AGN had pyodermatitis while the other had septic pleural effusion.
The patient who presented with pregnancy related nephropathy had two previous abortions, HBP, proteinuria and hyperuricemia.
For various reasons, the renal biopsy could not be performed except on five patients (22.7%) (three AS and two SS patients). The findings in the three AS patients were membranoproliferative glomerulonephritis (MPGN), focal and segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). CTIN was the finding in the two Hb SS patients. The outcome was favourable in the three AS patients contrary to the SS patients who progressed to end-stage renal disease within three months of presentation.
Therapy of our patients included several approaches. The two patients with a FSGS and a MGN benefited from oral corticosteroids treatment (1mg/kg/day over three months) in addition to monthly pulses of one gram cyclophosphamide.
The course was favourable for patients with AGN and pregnancy nephropathy. There were three patients with isolated proteinuria who were treated by captopril, an angiotensin converting enzyme inhibitor, 12.5 mg/day.
We lost nine patients to follow-up; of whom six had advanced CRF. Two patients with SS disease are receiving chronic hemodialysis.
| Discussion|| |
Prevalence of SCD is estimated as 8-10% in Senegal.  The usual renal manifestation of the SS disease include defect of urine concentration, distal tubular acidosis, abnormal proximal tubular function and increased glomerular filtration rate.  The primary event appears to be sickling of erythrocytes in the vasa recta capillaries in the medulla. The normal medullary environment plays an important role in this process, because it has both low oxygen tension and high osmolality.  Congestion and stasis in the vasa recta capillaries may lead to focal areas of hemorrhage or necrosis. Ultimately, this results in to interstitial inflammation and fibrosis, tubular atrophy, and papillary infarcts due to the vascular lesions. , These lesions are more severe in the SS than in the AS patients.
Microscopic or gross painless hematuria, due to papillary necrosis, is a sign frequently reported in AS patient.  The hematuria is usually unilateral with the left kidney four times more frequently involved than the right. This fact may be explained by increased venous pressure due to greater length of the left renal vein.  We did not encounter any case of isolated hematuria in our series. Papillary necrosis can be detected in SCD by intravenous urography even in asymptomatic patients. ,,
In the 1950s, Etteldorf et al  noted the increased glomerular filtration rate (GFR) in children with SCD. This appears to be mediated by vasodilator prostaglandins and can be reversed by the administration of nonsteroidal anti-inflammatory drugs.  Hyperfiltration coupled with glomerular hypertrophy can lead to glomerulosclerosis. ,
Isolated proteinuria in SCD is a marker of renal abnormalities; it was present in three patients in our study. In a pediatric prospective study, the prevalence of the isolated persistent proteinuria was 6.2% in the SS patients.  Moreover, microalbuminuria is prevalent in SS in children at age of seven years (26.5%) and increases to 46% in the 2nd decade of life. 
The nephrotic syndrome is found in 40% of patients with SCD. , Falk and Jennett  suggested that the NS in SCD was a predictor of progression to chronic renal failure. All degrees of proteinuria can be caused by microvascular obstruction that results in high transglomerular filtration pressure. This concept is supported by the decrease in protein excretion observed with the administration of ACE inhibitors. ,
Different glomerular lesions have been described in the NS related to SCD. Pardo  reported seven SCD patients who presented with MPGN and immune complex deposits (IgG, and C3). The proposed mechanism includes ischemic tubular injury that results in an inflammatory process and immune response.  One of our study patients had MPGN. Okoro reported MPGN in one out of three renal biopsies in Nigerian children with homozygous SCD.}  The cases of AGN reported in our study similar to others in the literature seem to be the classic postinfectious AGN.  In our study, at least one of the two cases of MGN seems to be secondary SCD. Kleinknecht et al  noted three SCD cases with MGN that were associated with antecedent streptococcal infection and extra renal manifestations.
FSGS is the most frequently encountered glomerular lesion in the homozygous SCD. Several mechanisms were implicated in the genesis of this lesion that included hyperfiltration and glomerular hypertrophy. , Falk et al  observed eight cases of FSGS in 10 renal biopsies whereas we noted one case of FSGS in five biopsies.
The incidence of hypertension (HTN) in patients with the SS disease is 2-6% compared with the incidence of 28% for the black population in United States. Loss of salt  and a possible defect of vascular tone in SCD 21 may explain the low incidence of HTN. Data from the cooperative study of sickle cell disease confirmed that individuals with SCD have significantly lower blood pressure than the general population.  In our study, HTN was found in 36% (8 cases on 22) of the patients that could be due to the high prevalence of CRF and/or high sodium diet.
The diagnosis of CTIN encountered in our study could be explained by the use of analgesic drugs,  repeated infections or traditional medicine abuse. This last factor is present in most of our patients and may lead to tubulointerstitial lesions. 
Acute nonoliguric renal failure (ARF) is present in 10% of patients hospitalized with SCD.  The patients with SCD are prone to ARF during periods of hypoxia, hypotension, acidosis, anaesthesia or intense physical efforts. Furthermore, renal venous thrombosis and intravascular hemolysis have been reported.  We did not have any case of ARF in our study.
In SCD, end-stage renal disease (ESRD) often occurs between the third and fifth decades of life. , The presence of the NS is a clinical marker for glomerulosclerosis and progression to ESRD. 2 CRF was the most frequent finding in our study probably due to the absence of proper screening of the renal diseases in our region. It is the second cause of mortality after the cerebrovascular accidents in older patients with SCD in Jamaica.  Powars  reported 4.2% incidence of CRF in a cohort of 750 patients with SCD followed during 25 years. The median survival after renal failure was 4 years. Hemodialysis is often proposed for the patients in ESRD. ,, Ojo  performed a comparative study of patients and allograft outcomes among African American kidney transplant recipients with ESRD as a result of SCD (n=82) and all other causes (n=22). The short term renal allograft result in recipients was 78% was and 77%, respectively. However, the long term outcome was comparatively diminished (48% versus 60%). There was a trend toward better patient survival with renal transplantation in comparison to dialysis.
Since the first description of medullary renal cancer in SCD patients by Baron et al in 1994,  about sixty cases have been reported.  All these patients were black except one of white race.  Davis et al  described a highly malignant and aggressive kidney tumor that appears to uniquely affect heterozygous SCD patients. It often presents as painful gross hematuria. The course of medullary carcinoma has not been modified with different immuno- and chemotherapies.  No case of this tumor was found in our study.
We conclude that there are various renal abnormalities in patients with SCD. Their management requires early screening and a multidisciplinary follow-up. The prognosis is very guarded in countries with high prevalence and without the availability of adequate program of dialysis and renal transplantation.
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