In this article, we mainly study the renal disorders of sickle cell disease, which remains the most frequent and serious hemoglobinopathy. We will simply mention the renal complications of thalassemia, whose prognosis is very different.
Kidney and sickle cell disease:
Until recently, sickle cell disease was mostly familiar to pediatricians and some molecular biologists.
However, better management of homozygous patients has significantly improved their prognosis and exceeded the fourth decade. Their long-term evolution remains complicated by organ failure, particularly renal failure. Its frequency, from 4.2 to 18%, increases with the quality of the initial care.
End-stage renal disease (ESRD) is not a very good prognosis and seems inevitable in patients who develop a nephrotic syndrome. Their long-term survival in hemodialysis and transplantation remains poor, which calls for a better understanding of the pathophysiology of kidney damage to provide the most preventative attitude possible.
Sickle cell disease affects, in its homozygous form, from 0.8 to 3% of West Indian subjects, and in its heterozygote variety, from 7 to 13%. The prevalence of renal failure is poorly understood and could reach 5 to 18% of the sickle cell population.
Many studies do not differentiate AS and SS patients with AS, making kidney risk analysis difficult in both groups, a risk that is naturally greater in homozygous patients.
In a case-control study of homozygous patients with Powars, 32 patients, or 4.2%, had chronic renal failure (CRF).The mean age at the time of diagnosis of renal impairment, the average survival at the stage of IRT and the age of death, despite the techniques of renal replacement, are 25 years, 4 years and 27 years, respectively. hence, the prognostic severity of renal impairment. Proteinuria, high blood pressure (hypertension), severe anemia and hematuria have been shown to be predictors of CKD.
In the 964 Platt series, the presence of CKD represented a major risk of early mortality. For other authors, episodes of tricorporeal postpubertal priapism were a risk factor for multiple organ failure, particularly renal failure.
The true incidence of IRT is poorly known because of early mortality bias. However, between 1992 and 1996, 345 new cases of IRT in the US population were listed.
Glomerular Function and Renal Blood Flow:
Several studies have shown that in young Sickle Cell patients, renal blood and plasma flow, as well as glomerular filtration rate (GFR), are increased by more than 50%. These abnormalities may persist until adulthood and may be related to compensatory hypersecretion of vasodilator prostaglandins in response to sickling.
Indomethacin reduces GFR by 10 to 20% in these patients, but not in controls. These hemodynamic changes may lead to renal tubular dysfunction and especially the development of a nephrotic syndrome due to severe severe segmental and focal glomerulosclerosis (GSF) lesions, leading to hyperfiltration CRI.
Guasch found an association between renal failure and decreased ultrafiltration coefficient in sickle cell patients. In addition, the study of fractional clearance of albumin and immunoglobulin (Ig) G seems to attest to an inverse correlation between ultrafiltration coefficient and glomerular permeability. This coefficient appears to be reduced in proteinuric patients with normal GFR, suggesting that the presence of albuminuria, or even nephrotic syndrome, is predictive of renal failure. However, in a more recent study, Schmitt suggests that increased transglomerular trafficking of macromolecules, decreased glomerular permeability, and increased ultrafiltration coefficient (Kf1), associated with glomerular hypertrophy-induced podocytic lesions, could be the cause of segmental and focal hyalinosis lesions of sickle cell patients with proteinuria. The apparent contradiction with Guasch’s study is that his patients had a lower GFR and greater proteinuria. The authors thus assume that the increase in Kf occurs at a very early stage in glomerulosclerosis lesions, then decreases, contributing to the fall of GFR.
In recent years, since the discovery of the important role of nitric oxide (NO) in animal and human physiology, a relationship has been established between increased NO synthesis and glomerular hyperfiltration in experimental models of nephropathy. sickle cell. Recently, Bank’s team investigated the mechanism of hyperfiltration in a mouse model of sickle cell, without taking into account the variable of anemia.
Their conclusion seems to confirm that NO synthesis via the N-arginine pathway is increased and positively correlated with GFR. The authors suggest that the increased synthesis of NOS II (NO synthetase) leads to vasodilation, and thus to renal hyperperfusion. The same group, by exposing sickle cell transgenic mice to chronic hypoxia, confirms that there is an activation of the NO synthase (iNOS), formation of free radicals and superoxide ions, responsible for an increase of the apoptosis . However, apoptosis by ischemia-reperfusion may induce tubulo-interstitial lesions and, secondarily, nephron amputation. It only remains to demonstrate that this mechanism exists in humans …
Some genetic studies suggest that the association with alphathalassemia may have a renoprotective role with a low prevalence of proteinuria and lower mean arterial blood pressure than patients with the intact alphaglobin gene.
Proximal tubular abnormalities:
The existence of early glomerular hyperfiltration, from childhood, will stimulate proximal tubular functions. Thus, hypersecretion of tubular creatinine is such that the measured creatinine clearance is overestimated by 25% or more in young patients.
Similarly, the clearance of uric acid is high, allowing maintenance of normal uricemia, while there is a hyperproduction of uric acid secondary to hemolysis. This hyperuricemia appears only later, during the decrease in glomerular filtration, in parallel with the evolution of CKD.
The proximal tubular reabsorption of sodium and phosphates is also high in these patients, which is evidence of an adaptation of tubuloglomerular feedback to glomerular hyperfiltration.
Distal tubular abnormalities:
· Functions of concentration
Hatch first demonstrated that there is a defect in concentration functions in sickle cell patients, regardless of their genotype, SS, AS or SC.
In young patients, not in adults, transfusions completely restore the possibilities of concentration.
The explanation usually evoked in children is that sludge in the vasa recta, caused by contact with the relative hypertonicity of the medulla interna, disrupts the normal functioning of the system against the current, limiting the concentration function. This anomaly appears to be reversible, at least partially, by indomethacin. Normal blood transfusion will decrease the fraction of sick cells passing through the vasa recta, thus improving the viscosity and flow rate of the internal medullary microperfusion. The reversibility of these disturbances by transfusion in young patients and the similarity of the lesions observed in papillectomized rats led to talk of a state of “functional papillectomy”.
In contrast, failure of transfusions to correct for concentration power abnormalities in older patients suggests that anatomical lesions become irreversible. In fact, studies in microangioradiography have shown that, with age, vasa recta become completely clogged, leading to a loss of juxtamedullary nephrons whose long portion of the Henle loop is required for water preservation. . The capillaries of the outer medulla and the cortical nephrons seem less susceptible to sickling lesions, thus preserving their dilution capacity. Thus, the maximum urinary osmolality in homozygous adults is 400 to 450 mOsm / kg.
Clinically, this defect of renal concentration is, except sometimes in the case of polyuropolydipsia, usually non-symptomatic. In children, it can magnify enuresis, or even promote dehydration, and therefore the onset of vasocclusive attacks, especially during episodes of diarrhea or severe vomiting.
· Decreased secretory and potassium excretion powers Some patients with sickle cell disease may develop a distal form of incomplete tubular acidosis. Thus, in 1968, authors describe eight Jamaican patients with an abnormal urinary pH response in the classical acidification test with ammonium chloride. Oster, in 1976, found a similar defect in six out of 20 patients with SS homozygous sickle cell disease. However, unlike hereditary type I renal tubular acidosis, there is neither hypokalemia nor hypercalciuria or nephrocalcinosis.
In 1979, Defronzo reported in some of his sickle cell patients a decreased excretion of potassium, with normal glomerular filtration, associated with a lack of acidification, and without altering the renin-angiotensin-aldosterone axis.Batlle described six observations of sickle cell patients who developed both hyperkalemia and hyperchloremic metabolic acidosis, five of whom clearly had renal impairment between 1.5 and 5.1 mg / dL creatinine. Cases were classified either as hyperkalemic distal tubular acidosis (failure to lower urinary pH) or as elective aldosterone deficiency (normal lowering of urinary pH, reduced ammonium extraction, inappropriate hypoaldosteronism); one patient had both deficits, four tubular renal hyperkalemic distal acidosis and the last a selective aldosterone deficiency.
The observed abnormalities may be due to ischemic lesions of the distal segment of the nephron, but the role of beta-adrenergic stimulation is possible.
The clinical manifestations of these pathophysiological processes are now well known and can occur at any time.
Asymptomatic hematuria is one of the most common symptoms of the disease, whether the patient is homozygous or not, at any age. Microscopic hematuria can be chronic, punctuated by episodes of gross hematuria.
It results from microthrombotic infarction, with extravasation of blood in the medullary internal and renal papillae, seats of a hypertonic medium and relatively hypoxic, favoring sickling in adjacent vasa recta. Microscopic hematuria, more common in men than in women, can be bilateral, with a predominance of the left side.
The importance of hematuria may, in some cases, require transfusion, or even lead to clotting with obstruction of the urinary shaft and renal colic chart. Elsewhere, a pyuria accompanies the hematuria, being able to discuss the diagnosis of acute pyelonephritis. Most often, the bleeding disappears spontaneously, but it can persist for weeks or even months.
Finally, exceptionally, it sits in subcapsular, or even extends in the perinephric space.
Therapeutically, different measures may be prescribed depending on the extent of the bleeding, ranging from hyperhydration, alkalinization, diuretics, hyperoxygenation hyperbaric chamber, pyelocalicielle irrigation by silver nitrate , nephrectomy as a last resort, even autotransplantation. The initial enthusiasm for using the urokinase inhibitor Epsilon-aminocaproic acid was based on the results of Black’s only work, which were not subsequently confirmed.
Complication described in 1963, it can occur in homozygous or heterozygous patients. Most often, it is diagnosed retrospectively, during an imaging test, by intravenous urography, ultrasound, CT scan or magnetic resonance imaging. In a detailed series, Vaamonde found 131 cases of papillary necrosis in 334 patients with homozygous sickle cell disease (39%), the incidence being 23 to 67% in the individual series. In most cases, there is no symptomatology or simply microscopic hematuria suggesting that the incidence is probably underestimated. The average age of discovery is 21 ± 1 year, extremes of 4 to 68 years.
Clinically, macroscopic painful hematuria is the most common presentation. Sometimes, it can cause a picture of renal colic, papillary necrosis creating a ureteral barrier, infection or sepsis and / or acute renal failure. Elsewhere, the combination of pyuria, hematuria and lumbago causes an episode of acute pyelonephritis; urine sediment analysis and bacteriological examination of the urine correct the diagnosis.
The sickling of red blood cells in the vasa recta can induce a medullary infarction with extravasation of erythrocytes.
In the renal medulla, and particularly in the papilla, this sickling is favored by the hypertonicity, the hypoxia and the acidic pH reigning locally. Since the kidney is particularly oxygen-consuming, it remains very susceptible to tissue hypoxia caused by sickling and hyperviscosity of red blood cells in the renal microcirculation. It is therefore not surprising that functional and anatomical renal lesions appear in these areas. On rare occasions, papillary necrosis may cause cortical infarction with or without development of perirenal hematoma. Some authors have classified papillary necrosis according to their severity. Histological examination of autopsy nephrectomy specimens revealed perinecrotic areas surrounded by leukocytes and polynuclear cells in the medulla and papillae. Vascular congestion with edema, infarction and necrosis in the papillary region is associated with chronic interstitial nephritis-type lesions with fibrosis and tubular atrophy. The thickness of the cortex can be reduced, sometimes with the presence of micro-abscess, or even frank cortical necrosis, which remains exceptional. Despite the importance of these lesions, progressive interstitial nephritis leading to IRT is rare, perhaps because the lesions are more localized, with a lower rate of infection than in papillary necrosis induced by nephropathy. analgesics.
Regulation of blood pressure:
The prevalence of hypertension in black Americans is around 30%. However, when sickle cell patients are matched by sex and age to controls, the prevalence of systolic and diastolic hypertension is lower in sickle cell patients than in the control population. Thus, the prevalence of hypertension in the sickle cell population of 187 Johnson’s Los Angeles patients is only 3.2%. By adjusting for age and sex, the difference in blood pressure persists in all age groups (10 to 20 mmHg for systolic and diastolic) between the sickle cell group and healthy individuals. In the Sklar experiment, hypertension developed in sickle cell patients only in advanced renal failure. These facts are relatively surprising with regard to vasculopathy induced by sickle cell disease, and the notion of hypertension secondary to renal vascular stenosis and thrombosis. On the other hand, the blood pressure of sickle cell patients is on average higher than that of thalassemic patients with the same degree of anemia.
This “relative” hypotension, cause or consequence of renal abnormalities in sickle cell patients, is currently not very clear. Some mention the decrease in peripheral resistance in case of anemia by release of endogenous vasodilator substances (prostaglandins and NO) to correct tissue hypoxia. In addition, there is probably some degree of mandatory salt loss accentuated by the increase in renal blood flow described above, combined with the natriuretic effect of prostaglandins. Hatch reports high renin levels and a diminished response to the vasoconstrictor effects of angiotensin in these patients. These observations are similar to those found in Bartter’s syndrome, another situation in which patients are normotensive, with high renin levels, associated with a relative excess of vasodilator prostaglandins.
Physiology of erythropoietin:
The level of endogenous erythropoietin is high in sickle cell patients, but not as much as in other situations where anemia is so severe. Among the explanations, it was mentioned the lack of affinity for oxygen S cells to reduce tissue hypoxia and more marked increase in cardiac output. It is also possible that renal synthesis of erythropoietin by tubular cells is disrupted by falciformally induced hemodynamic intrarenal factors.
Finally, the creatinine level, lowered in sickle cell patients, as well as the reduction of their muscle mass may mask kidney failure, particularly in the elderly, which may be a cause of so-called “inadequate” response of erythropoietin.
The pharmacological doses of erythropoietin prescribed in dialysis patients do not result in a significant hematologic response. However, Steinberg reported the possibility of correcting the hematocrit of these patients with very high doses of erythropoietin, while Sklar, at doses of 450 U / kg three times a week, found, in sickle cell patients homozygous, heterozygous or associated with betathalassemia, than a moderate decrease in transfusion
The hypothesis of a circulating inhibitor has been evoked to explain in part this pseudoresistance to erythropoietin.
In contrast, a successful kidney transplant corrects the hematocrit which returns to the level of pre-urinary values.
Acute renal failure :
Considering the multiple renal abnormalities described above in these patients, their susceptibility to developing severe infections, their predisposition to volume depletion and the wide use of potentially nephrotoxic drugs, it is surprising that the literature does not yield more than of acute renal failure, the first case being secondary to rhabdomyolysis. Since then, several authors have described such cases, including military training in young recruits with sickle cell disease. In this study, the risk of sudden death was 28 times greater in black soldiers with sickle cell disease, with some deaths attributed to rhabdomyolysis, stroke, cardiac arrest, or arrhythmia.
However, excellent hydration has been shown to prevent malignant hyperthermia and to reduce the risk of sudden death.
Since 1985, several cases of non-traumatic rhabdomyolysis have been reported during severe vaso-occlusive attacks, this complication being more frequent in systemic disorders, particularly thoracic, hepatic, or episodes of acute renal failure.
Sklar, in 1990, attempted to specify the incidence of acute renal failure in 116 hospitalized sickle cell patients; 12 of the 116 patients (10.3%) had at least a doubling of their serum creatinine. In most cases, infection is the main reason for admission, while volume depletion is the most common identifiable cause of kidney failure. Two of the three most severely affected patients required dialysis. Ten of the 12 patients survived.
Sickle cell nephropathy:
In recent years, many studies have been done on a particular kidney entity of sickle cell disease, called sickle cell nephropathy. The latter is defined by the appearance of a proteinuria evolving towards a table of nephrotic syndrome and an IRT.
Incidence of proteinuria:
In many studies, proteinuria has been studied by semi-quantitative methods, such as the 0 to 4 cross protein test strip.Henderson, in 1950, is the first to report the prevalence of proteinuria in sickle cell disease, which he said was 31% in 54 patients. Other authors find a prevalence varying between 15% and 26%. In all of these studies, the incidence of proteinuria increases with age and is associated with impaired renal function.
In 1985, Tejani reported a series of 13 children with proteinuria or nephrotic syndrome whose predominant lesions are segmental and focal hyalinosis. Bakir, in 1987, reported a series of 12 sickle cell patients with nephrotic syndrome and found 37 cases in the literature.
Bernstein was the first to describe glomerular hypertrophy in patients with sickle cell nephropathy. Since then, other authors have confirmed this type of lesions and have also described the existence of focal glomerulosclerosis. Most studies have been done in patients with advanced forms of nephropathy, autopsy, or renal biopsy. Falk, in 1992, reported a series of ten patients with SS hemoglobinopathy who had a proteinuria of between 0.8 and 10.8 g / 24 hours associated with renal failure defined by serum creatinine less than 177 mmol / L. The most obvious anatomical changes were dominated by glomerular hypertrophy and GSF at the vascular pole.
In light microscopy, examination of non-sclerotic glomeruli revealed hypertrophy and an increase in the number of capillary lumens as well as proliferation of epithelial, endothelial and mesangial cells. The area and mean glomerular diameter are significantly increased in patients with sickle cell disease compared to a control group of 10 patients.Interstitial fibrosis and tubular atrophy are often associated with the presence of glomerulosclerosis. In the Falk series, there are abundant granules of hemosiderin in the cytoplasm of tubular epithelial cells and the lumen of vessels contains deformed red blood cells due to in vitro sickling.
Immunofluorescence examination did not reveal immune complex deposits, except for irregular IgM and C3 fixation on sclerous lesions, which is typical in segmental and focal hyalinosis lesions.
The electron microscopic examination confirms the absence of immune deposits and found an erasure of the foot of the podocytes, as well as a moderate focal expansion of the subendothelial zone, which is also usual in this type of glomerulopathy.
In sum, the general impression of these studies suggests that the initial lesions of sickle cell nephropathy begin with glomerular hypertrophy with progressive development of a predominant GSF at the vascular pole. Others, such as Strauss and Ozawa, considered that sickle cell glomerulopathy was an autologous immune complex deposition disease. These immune deposits are thought to be related to glomerular deposition of antibodies associated with tubular epithelial antigens. However, the immunological arguments remain quite modest, since, in other studies such as Falk’s, no immune deposits were found on early biopsies.
Other types of glomerulonephritis have been reported, including post-streptococcal glomerulonephritis, extramembranous glomerulonephritis, and membranoproliferative glomerulonephritis.
Contrary to the initial descriptions of poststreptococcal glomerulonephritis, there does not appear to be an increase in incidence in these patients. Likewise, it has not been confirmed that a type of immune complex glomerulonephritis predominates in sickle cell patients, especially since during sickle cell nephropathy progressive glomerular lesions similar to those of membranoproliferative glomerulonephritis or thrombotic microangiopathy, sometimes associated with segmental and focal hyalinosis. The cause of these lesions is not known but may be related to chronic endothelial lesions or mesangial phagocytosis of sickled and fragmented red blood cells.
An authentic membranoproliferative glomerulonephritis type I is rare in patients with sickle cell disease, but may exist, differing from other sickle cell nephropathies by the existence of immune complex deposits, demonstrated by immunofluorescence and examination by electron microscopy .
Chronic renal failure and prognostic factors:
Thomas was the first to confirm that kidney damage contributes to mortality in elderly sickle cell patients. Kidney failure is responsible for the mortality of 17 of 95 patients over the age of 20, or 18%. An HTA, unusual in these patients, is typical in the group with renal failure. Sklar found a prevalence of 4.6% CKD on his cohort of 368 patients. The increase in the prevalence of proteinuria and renal failure with age is evident.
Powars reported a prospective 25-year study of CKD in 725 homozygous sickle cell and 209 heterozygous patients.Renal failure was diagnosed in 4.2% of homozygotes against 2.4% of heterozygotes. The diagnosis was made earlier in homozygous patients, at the age of 23.1 years against 49.9 years. The relative risk of mortality in the homozygous group with renal failure is 1.42. The case-control analysis of the renal failure group (n = 36) found poor prognostic factors for nephropathy such as proteinuria, hematuria, hypertension, nephrotic syndrome and the severity of anemia.
Platte, in 1994, reported data from the multicenter cooperative study of sickle cell disease, including 3,764 patients of all ages. According to this study, 18% of adult mortality is associated with chronic organic failures related to sickle cell disease; 22 of these 38 deaths occurred in patients with CKD.
RENAL MEDICINAL CARCINOMA:
Renal cell carcinoma is one of the possible evolutionary complications. Its incidence in the sickle cell population is 1.74 / 1000 patients per year. The mortality rate is 1.04 cases per year / patient. These figures, however, are comparable to those reported in black Americans aged 35 to 40, with an incidence of 1.9 / 1000 per year / patient.
Baron was the first to suspect this type of tumor during sickle cell disease. His data has been confirmed by Davis.
In the original series of 33 Davis patients, both sexes are consistently affected after 25 years. All patients whose ethnic group is specified (n = 25) are black. Macroscopic hematuria and lower back pain are the most common symptoms, in contrast to weight loss and the presence of a palpable tumor mass. In 13 patients, the mean duration of symptomatology is 8 weeks; in 19 patients, survival after surgery is 15 weeks, indicating the aggressiveness of the tumor.
Histological studies mainly concern the right kidney (23 out of 33 patients) and show an invasion of the cortex and perinephreotic tissues with, within the tumor, hemorrhagic necrotic zones.
The association of sickle cell disease in young patients with renal cell carcinoma has suggested the role of a genetic factor. Several arguments plead in this direction. A cytogenetic study on tumor samples was performed by Avery in a 30-year-old American black man: all abnormal cells had a chromosome 11 monosomy; two cells contained chromosome 3 abnormalities (monosomy and translocation).
However, other types of neoplasia are known to be related to the loss of a chromosome 11 allele, and cases of familial renal cell carcinoma or associations between von Hippel Lindau syndrome and renal carcinoma have been reported in young people. patients related to chromosome 3 abnormalities.
The medullary carcinoma remains a serious aggressive cancer whose evolution has hardly been modified by the new therapeutic approaches. It should be looked for in sickle cell patients at the earliest stage. A renal ultrasound should, in our opinion, be part of the systematic annual surveillance review.
TREATMENT OF NEPHROPATHY AND TERMINAL RENAL FAILURE:
Support for tubular anomalies:
The defect usually subclinical concentration does not require specific treatment, except a good hydration largely alkaline to compensate for a possible incipient acidosis, which must be increased during vaso-occlusive crises.
A restriction in potassium and phosphorus intake is necessary in case of evolution towards the IRC, as well as the prescription of allopurinol in case of gouty access by hyperuricemia.
In some cases, thiazides or loop diuretics are useful for increasing potassium excretion. Potentially hyperkalaemic drugs, particularly ACE inhibitors, nonsteroidal anti-inflammatory drugs, beta-blockers and heparin, should be prescribed with caution in these patients, especially in renal failure. . Finally, especially in patients infected with the human immunodeficiency virus (HIV) and suffering from pneumocystosis, the prescription of sulfamethroprime and pentamidine should be careful, because of the amiloride-like effect on distal potassium secretion .
Sickle cell nephropathy:
In recent years, proteinuria, nephrotic syndrome and IRC leading to IRT have been increasing in frequency.
Unfortunately, the physiopathogenic mechanisms (see above) and their therapeutic implications remain unclear.
The efficacy of nonsteroidal anti-inflammatory drugs has not been demonstrated, nor has immunosuppressive heroic therapies such as corticosteroids and cyclophosphamide been shown to be effective. In the CKD stage, protein restriction is difficult to maintain and advocate in these partially already undernourished patients. Based on experimental and clinical data confirming glomerular hyperfiltration as seen in diabetic nephropathies, about ten selected patients with moderate renal insufficiency related to segmental and focal hyalinosis lesions demonstrated on biopsy. , were treated with enalapril (at a dose of 5 mg to 10 mg / day). At constant blood pressure, the treatment appeared to reduce their nephrotic syndrome, but the latter recurred as soon as the therapy was stopped.
The effect of angiotensin II receptor blockers has not yet been evaluated. Data on the effects of ACE inhibitors and angiotensin II receptor blockers on proteinuria and progression of IRT are still limited, especially as proteinuria is associated with faster renal function degradation. Furthermore, the long-term effects of ACE inhibitors and angiotensin II receptor blockers on alterations in intraglomerular hemodynamics, as well as the reversibility of segmental and focal hyalinosis lesions, have not been fully demonstrated in these patients. .
In different models of segmental and focal hyalinosis kidney, the protective effect of ACE inhibitors and angiotensin II receptor antagonists on proteinuria appears to be independent of hemodynamic changes, whereas the long-term effect on Segmental and focal hyalinosis lesions appear to be related to control of systemic and intraglomerular pressures.
Thus, in five-sixths nephrectomized rats, Ots studied the nephroprotective effect of enalapril, losartan, or a combination of both. He concludes that there is a correlation between increased blood pressure and worsening segmental and focal hyalinosis lesions. However, at comparable blood pressure, he did not notice any difference in the frequency of glomerular lesions between different groups.
The indication of these therapies remains justified, but with caution, given the risk of hyperkalemia, especially in case of CKD.
In 1974, Frydeman reported the first case of therapeutic success and long-term survival of dialysis sickle cell disease.
Both dialysis techniques were used, peritoneal dialysis and hemodialysis. However, the total number of patients treated remains modest.
Nissenson, using US data from 1983 to 1985, found during these 3 years 77 cases treated by dialysis (SS and AS);96% of the subjects are black, 60% are men, 57% are aged 20 to 39 at the time of the diagnosis of IRT and 39% of 40 to 59 years; 82% were initially treated with hemodialysis, 17% with continuous ambulatory peritoneal dialysis and 1% with cadaver kidney transplantation. At 30 months of treatment, 59% of patients are alive. These results seem similar to those of other chronic systemic diseases such as diabetes. Curiously, the dialysis technique itself does not appear to influence the frequency of vaso-occlusive seizures, whereas one might think that the tendency to hypoxemia, arterial hypotension and activation of the various cytokines triggered by dialytic phenomena, especially in hemodialysis, could cause a sludge phenomenon and thus vaso-occlusive attacks.
The experience of kidney transplantation remains limited in this population. Chatterjee, in two short-term studies, shows that patient and graft survival is comparable to a non-sickle cell population. In 1980, 34 kidney transplants were performed in 30 sickle cell patients. Survival at 1 year is 87% for patients, 67% for the graft. In the 1987 data, 45 kidney transplants were recorded in 40 patients, with at 1 year a patient survival rate of 88% and graft of 67%. At 1 year, the graft survival rate in patients with live donors is 82%, compared to 62% with cadaver kidneys. It is important to note that most patients are heterozygous (70% in 1980, 67.5% in 1987), treated before the ciclosporin era, and that their hemoglobinopathy was an aggravating factor and not a factor. main origin of their IRT.
From these studies, it appears that sickle cell disease should not be a formal contraindication to renal transplantation.Recently, Ojo published the results of patient and graft follow-up in sickle cell patients compared to black American transplant patients of the same age, and for other causes. This very important study reports the fate of 22 647 American Blacks in IRT, some with sickle cell nephropathy, who received a single kidney between 1984 and 1996. Only 82 patients, or 0.4%, had as their only cause their IRT a sickle cell nephropathy, 81 had SS hemoglobin and only one heterozygous sickle cell disease. Survival of cadaver or living donor at 1 year is similar between sickle cell and non-sickle cell (78% vs. 77%). However, survival of the cadaver graft at 3 years is significantly lower in sickle cell patients: 48% against 60% for other patients. Sickle cell survival was also lower at 1 year (78% vs. 90%) and 3 years (59% vs. 81%). However, other analyzes seem to show better survival of transplant patients compared to dialysis patients waiting for transplantation. Ojo suggests suggesting a transplant for this indication, arguing that the high mortality rate was due more to the complications of the disease itself than to the side effects of the immunosuppressive therapy needed for transplantation. In his study, the survival of transplanted sickle cell patients had a median duration of 33 months. In addition, the mortality rate was over 50% at 2 years in patients with CKD and / or nephrotic syndrome.
Despite these encouraging results in relation to hemodialysis, other morbidity factors should not be overlooked, since vasocclusive attacks are more frequent in the transplanted patient, probably favored by an increase in endogenous hematopoiesis, with consequently an increase in blood viscosity. Some advocate the use of hydroxyurea to increase hemoglobin F and decrease the frequency of seizures that can sometimes be induced by the use of monoclonal antibodies such as OKT3. Finally, recurrences of sickle cell nephropathy on grafts were reported at 3.5 and 4.5 years post-transplant.
Innovations in immunosuppressive therapeutics should broaden the indications for transplantation in these patients.Finally, marrow transplantation, or even gene therapy, may be able to avoid the long-term complications of the disease, especially the progression to renal failure, or at least to decrease its progression.
Kidney and thalassemias:
Thalassemias are the consequence of a lack of synthesis of globin chains. They can present in several forms: alpha-thalassemias, due to a deficit of synthesis of the alpha chain which are the most frequent; beta-thalassemias, secondary to a synthesis deficit of the beta chain. Only the most severe forms can be complicated by kidney damage.
Renal complications in patients with thalassemia resemble those in sickle cell patients, but to a lesser degree, with no progression to renal failure in most cases, except in association with sickle cell disease.
They are dominated by a defect of urinary concentration and tubular acidosis due to organic lesions by deposition of hemosiderin in the proximal and distal tubule confirmed on autopsies. Tissue iron excess, which is common in thalassemic patients, has been shown to be responsible for an increase in lipid peroxidation, as reflected by plasma and urinary malondialdehyde (MDA) levels. A correlation between the level of plasma MDA and ferritinemia could thus be demonstrated.
Some authors have suggested that there is a higher incidence of glomerulopathies, especially endocapillary, in thalassemics, which may lead to TIR. However, these results have never been confirmed.
Acute renal failure:
Rare cases of acute renal failure have been reported following toxic doses of deferoxamine (Desferal t ) injected intravenously into thalassemic patients. The evolution was favorable in most cases, sometimes after some hemodialysis sessions.