NATURE OF CONCENTRATING DEFECT IN SICKLE-CELL NEPHROPATHY: Microradioangiographic Studies

doi:10.1016/S0140-6736(70)90836-6

The Lancet

Volume 295, Issue 7644, 28 February 1970, Pages 450-452

https://doi.org/10.1016/S0140-6736(70)90836-6 Get rights and content

Abstract

Microradioangiographic studies of sickle-cell kidneys reveal gross lesions of the vessels of the renal medulla, with almost complete absence of vasa recta in sickle-cell anaemia; and reduced number of vasa recta and loss of normal bundle architecture in sickle-cell trait and sickle-cell hæmoglobin-C disease. These findings suggest that the basic lesion in sickle-cell nephropathy is obliteration of vasa recta leading to the observed abnormalities in concentrating function, since these vessels form an intrinsic part of the counter-current multiplication system of the long loops of Henle.

References (13)

M.F. Levitt et al.
Am. J. Med.
(1960)
J.B. Herrick
Archs intern. Med.
(1910)
C.J.D. Zarafonetis et al.
J. Lab. clin Med.
(1954)
H.G. Keitel et al.
J clin. Invest.
(1956)
L. Schlitt et al.
Pediatrics, Springfield
(1960)
P.E. Perillie et al.
J. clin. Invest.
(1963)

There are more references available in the full text version of this article.

Cited by (127)

Sickle Cell Disease and the Kidney: Filters Gone Awry
2022, Hematology/Oncology Clinics of North America
Citation Excerpt :
This study showed that higher mean hemoglobin levels and higher percent fetal hemoglobin were associated with improved urinary concentration. Chronic transfusion may also be associated with preserved urine concentration ability, but randomized clinical trials have not been conducted to assess this outcome.3,10,11 The data suggest that transfusions earlier in life are more beneficial than when started after the first decade of life.
Sickle cell nephropathy. Clinical manifestations and new mechanisms involved in kidney injury
2021, Nefrologia
Citation Excerpt :
Individuals with sickle cell trait carry a single allele affected by the hemoglobinopathy S mutation, while the other allele is normal. As observed by renal microangiography, they present distortion and destruction of the vasa rectus, although considerably less than patients with SCD.46 However, according to a meta-analysis published in 2018, hematuria is 2 times more frequent than in SCD.17
Kidney problems are among the most common complications in sickle cell disease (SCD). They occur early in childhood and are one of the main factors related to mortality in these patients. The main underlying pathogenic mechanisms are vaso-occlusion and haemolysis. The renal medulla has ideal conditions for the sickling of red cells due to its low partial pressure of oxygen, high osmolarity and acidic pH. Initially, sickle-cell formation in the vasa recta of the renal medulla causes hyposthenuria. This is universal and appears in early childhood. Microscopic and macroscopic haematuria also occur, in part related to renal papillary necrosis when the infarcts are extensive. Release of prostaglandins in the renal medulla due to ischaemia leads to an increase in the glomerular filtration rate (GFR). Adaptively, sodium reabsorption in the proximal tubule increases, accompanied by increased creatinine secretion. Therefore, the GFR estimated from creatinine may be overestimated. Focal segmental glomerulosclerosis is the most common glomerular disease. Albuminuria is very common and reduction has been found in 72.8% of subjects treated with ACE inhibitors or ARB. Recent evidence suggests that free haemoglobin has harmful effects on podocytes, and may be a mechanism involved in impaired kidney function in these patients. These effects need to be better studied in SCD, as they could provide a therapeutic alternative in sickle cell nephropathy.
Las complicaciones renales se encuentran entre las más frecuentes de la enfermedad falciforme (EF), aparecen tempranamente desde la infancia y constituyen uno de los principales factores relacionados con la mortalidad en estos pacientes. La vasooclusión y la hemólisis son los principales mecanismos patogénicos subyacentes. La médula renal reúne condiciones ideales para la falciformación de los hematíes debido a su baja presión parcial de oxígeno, elevada osmolaridad, y pH ácido. Inicialmente, la falciformación en los vasa recta de la médula renal es la causa de hipostenuria, que es universal y aparece en la infancia temprana. Existe también hematuria, microscópica y macroscópica en parte relacionada con la necrosis papilar renal cuando los infartos son extensos. La liberación en la médula renal de prostaglandinas debido a la isquemia se relaciona con el aumento del filtrado glomerular (FG). De forma adaptativa, aumenta la reabsorción de sodio en el túbulo proximal, que se acompaña de un aumento de la secreción de creatinina. Por ello, el FG estimado a partir de la creatinina puede estar sobreestimado. La glomeruloesclerosis focal y segmentaria es la glomerulopatía más común. La albuminuria es muy frecuente y se ha observado reducción en el 72,8% de los sujetos tratados con IECAs o ARA-II. Recientes evidencias sugieren que la hemoglobina libre tiene efectos nocivos sobre los podocitos, pudiendo ser un mecanismo implicado en la alteración de función renal que presentan estos enfermos. Estos efectos han de ser mejor estudiados en la EF, ya que podrían constituir una alternativa terapéutica en la nefropatía falciforme.
Sickle cell disease: Clinical presentation and management of a global health challenge
2019, Blood Reviews
Citation Excerpt :
Vaso-occlusion causes ischaemia in the renal medulla. Contributing factors include volume depletion due to hyposthenuria, frequent and chronic use of non-steroidal anti-inflammatory drugs (NSAIDS), infections, massive haemolysis and rhabdomyolysis [150–152]. Recent studies have established an association between episodes of acute kidney injury and progression to chronic kidney disease [153–157].
Sickle cell disease is an autosomal recessive, multisystem disorder, characterised by chronic haemolytic anaemia, painful episodes of vaso-occlusion, progressive organ failure and a reduced life expectancy. Sickle cell disease is the most common monogenetic disease, with millions affected worldwide. In well-resourced countries, comprehensive care programs have increased life expectancy of sickle cell disease patients, with almost all infants surviving into adulthood. Therapeutic options for sickle cell disease patients are however, still scarce. Predictors of sickle cell disease severity and a better understanding of pathophysiology and (epi)genetic modifiers are warranted and could lead to more precise management and treatment. This review provides an extensive summary of the pathophysiology and management of sickle cell disease and encompasses the characteristics, complications and current and future treatment options of the disease.
Renal Sodium Gradient Orchestrates a Dynamic Antibacterial Defense Zone
2017, Cell
Lower urinary tract infections are among the most common human bacterial infections, but extension to the kidneys is rare. This has been attributed to mechanical forces, such as urine flow, that prevent the ascent of bladder microbes. Here, we show that the regional hypersalinity, required for the kidney’s urine-concentrating function, instructs epithelial cells to produce chemokines that localize monocyte-derived mononuclear phagocytes (MNPs) to the medulla. This hypersaline environment also increases the intrinsic bactericidal and neutrophil chemotactic activities of MNPs to generate a zone of defense. Because MNP positioning and function are dynamically regulated by the renal salt gradient, we find that patients with urinary concentrating defects are susceptible to kidney infection. Our work reveals a critical accessory role for the homeostatic function of a vital organ in optimizing tissue defense.
Renal papillary necrosis in patients with sickle cell disease: How to recognize this ‘forgotten’ diagnosis
2017, Journal of Pediatric Urology
Citation Excerpt :
This increased permeability will result in red blood cells leaking into the collecting system. Subsequently, the number of vasa recta will be reduced and the normal medullary architecture will be lost [11]. RPN has an incidence of up to 50% in patients with sickle cell trait.
Renal papillary necrosis is not commonly seen in daily practice, but can have severe consequences when it is not diagnosed in time. It is known to be associated with sickle cell hemoglobinopathies; however a wide range of etiologies are possible, and it is therefore not the first diagnosis clinicians consider in patients with sickle cell disease who present with hematuria.
A literature search was performed to summarize the current knowledge about renal papillary necrosis associated with sickle cell disease. These findings are illustrated with a case of a 9-year old girl with sickle cell disease who was referred with painless gross hematuria.
Typical radiologic signs for renal papillary necrosis are necrotic cavities that fill with contrast, small collections of contrast peripheral to the calyces in the papillary region (ball-on-tee sign), calcification of the papillary defect, filling defects, hydronephrosis, blunted papillary tip, clefts in the renal medulla filled with contrast, hyperattenuated medullary calcifications, non-enhanced lesions surrounded by rings of excreted contrast, and clubbed calyces.
This study focuses on the pathophysiology of renal papillary necrosis associated with sickle cell disease, the possible symptoms, as well as the diagnostic steps, with a special interest in particular presentation on old (retrograde pyelography) and new (computed tomography) gold standard in radiologic imaging, and the management for this pathology.
This study aims to remind clinicians of this “forgotten” diagnosis and what signs to look for in pediatric patients with sickle cell disease who present with hematuria. In pediatric cases radiation protection is important, therefore knowing what radiologic signs can be found on retrograde pyelography can lead to early identification of this pathology without having to proceed to computed tomography.
Sickle Cell Nephropathy
2017, National Kidney Foundation's Primer on Kidney Diseases
Sickle cell anemia is caused by the homozygous inheritance of the sickle β-globin gene and affects multiple organ systems. Because of its unique physiology, the kidney is particularly susceptible to injury in sickle cell disease (SCD). Individuals with SCD exhibit glomerular hyperfiltration and also present with urinary concentrating defects, hematuria, and overt papillary necrosis. As patients age, they are prone to developing sickle cell glomerulopathy and subsequent albuminuria and overt proteinuria. Low-level albuminuria may be present in up to 60% of sickle cell patients over the age of 35. Determination of chronic kidney disease (CKD) is somewhat impaired when using creatinine-based measures of the estimated glomerular filtration rate due to the hyperfiltration noted in these individuals. As CKD and end-stage kidney disease develop, sickle cell anemia poses some unique management challenges, including that of anemia management and kidney transplantation. The use of angiotensin-converting enzyme inhibitors may reduce proteinuria in SCD, but their long-term benefit remains unknown. Similarly, hydroxyurea has suggested, but unproven, benefit. Sickle cell trait (SCT), and less commonly SCD, is associated with renal medullary carcinoma, a rare and aggressive malignancy. Recent data have suggested that SCT, the heterozygous inheritance of the sickle β-globin gene, may be associated with CKD.

View all citing articles on Scopus

View full text

Preliminary CommunicationNATURE OF CONCENTRATING DEFECT IN SICKLE-CELL NEPHROPATHY: Microradioangiographic Studies

Abstract

Am. J. Med.

Archs intern. Med.

J. Lab. clin Med.

J clin. Invest.

Pediatrics, Springfield

J. clin. Invest.

Preliminary Communication
NATURE OF CONCENTRATING DEFECT IN SICKLE-CELL NEPHROPATHY: Microradioangiographic Studies