Calcification in end-stage kidneys

doi:10.1016/0002-9343(81)90255-2

The American Journal of Medicine

Volume 71, Issue 1, July 1981, Pages 33-37

https://doi.org/10.1016/0002-9343(81)90255-2 Get rights and content

Abstract

This study was carried out to determine the frequency and to quantitate the severity of calcium-phosphate deposits in end-stage kidneys. In 57 of 59 end-stage kidneys obtained from patients with a variety of different renal diseases, calcium levels were greater than 2 standard deviations (SD) above control values. The mean calcium concentration was 157 ± 24 mmol/kg dry defatted tissue in the end-stage kidneys as compared to 17 ± 1 mmol/kg in the control kidneys. Histologically, calcium was deposited in the cortical tubular cells, basement membranes and interstitium. It would appear that calcification occurred during the course of renal failure rather than terminally in that the kidney calcium concentration bore no relationship to the calcium × phosphate product, and the calcium concentration in the kidneys of uremic patients undergoing dialysis (144 ± 23 mmol/kg) was no greater than that found in uremic patients not undergoing dialysis (188 ± 62 mmol/kg). It is suggested that calcification may damage the diseased kidney accelerating the rate of renal functional deterioration.

References (23)

DC Britton et al.
Renal function following parathyroid surgery in primary hyper parathyroidism
Lancet
(1971)
ML Karlinsky et al.
Preservation of renal function in experimental glomerulonephritis
Kidney Int
(1980)
SR Contiguglia et al.
Nature of soft tissue calcification in uremia
Kidney Int
(1973)
E Slatopolsky et al.
On the prevention of secondary hyperparathyroidism in experimental chronic renal disease using proportional reduction of dietary phosphate intake
Kidney Int
(1972)
LS Ibels et al.
Arterial calcification and pathology in uremic patients undergoing dialysis
Am J Med
(1979)
VE Pollak et al.
Chronic renal disease with secondary hyperparathyroidism
Arch Intern Med
(1959)
AI Katz et al.
The place of subtotal parathyroidectomy in the management of patients with chronic renal failure
Trans Am Soc Artif Intern Organs
(1968)
AI Katz et al.
Secondary hyperparathyroidism and renal osteodystrophy in chronic renal failure. Analysis of 195 patients with observations on the effects of chronic dialysis, kidney transplantation and subtotal parathyroidectomy
Medicine (Baltimore)
(1969)
DC Kuzela et al.
Soft tissue calcification in chronic dialysis patients
Am J Pathol
(1977)
A Hecht et al.
Primary hyperparathyroidism. Laboratory and clinical data in 73 cases
JAMA
(1975)

M Hossain

Vitamin-D intoxication during treatment of hypoparathyroidism

Lancet

(1970)

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Nonneoplastic Diseases of the Kidney
2020, Urologic Surgical Pathology
In keeping with the spirit of Marcello Malpighi, this chapter also aspires to reveal “the manner of Nature’s operation” as it affects the kidney.¹ However, unlike Malpighi, today’s knowledge draws extensively on the labors, discoveries, and insights of investigators of the past centuries.
Knowledge of the normal structure and function of the kidney has been acquired over centuries of scholarly effort. We have come a long way since Aristotle taught that urine was formed by the bladder and that kidneys were present “not of actual necessity, but as matters of greater finish and perfection.”¹ Reference to the excretory functions of the bladders and kidneys can be found in early Indian Ayurveda, Chinese, or Egyptian literature.2, 3, 4 Some of the earliest scientifically valid experimental methods are described in The Canon of Medicine by the famous Persian Muslim physician Abu Ali Sina, also known as “Avicenna.”5, 6, 7, 8, 9, 10, 11, 12, 13 He meticulously described the layers of the bladder and its two-stage function, the intramural ureter and antireflux mechanisms, and scientifically classified urethral and bladder diseases, notably calculi. The foundation of modern urology was established in the sixteenth century by Leonardo da Vinci and Vesalius, who provided the first accurate and detailed drawings of the female and male genitourinary tracts (Fig. 1.1).14, 15 More than 300 years passed before William Bowman, in 1842, coupled intravascular dye injection with microscopic examination to demonstrate the structural organization of the nephron and its vascular supply (Fig. 1.2).16, 17 Bowman’s observations provided morphologic support for Malpighi’s seventeenth-century speculation of a filtration function for the malpighian body (the glomerulus).1, 18 Sixty years later the embryologic development of the nephron was demonstrated by Huber in a thin-section serial reconstruction study of embryos (Fig. 1.3).¹⁹ Huber’s observations were refined and elegantly illustrated by Brödel in 1907.²⁰
Renal matrix Gla protein expression increases progressively with CKD and predicts renal outcome
2018, Experimental and Molecular Pathology
Citation Excerpt :
Early experimental studies indicated that renal calcification may accelerate chronic kidney disease (CKD) progression (Lau, 1989; Cozzolino et al., 2002; Ibels et al., 1978). While several studies reported increased renal calcium content (Gimenez et al., 1987; Ibels et al., 1981) and microscopic nephrocalcinosis (Evenepoel et al., 2015) in human kidneys in advanced CKD, the idea of a direct effect of calcification on progressive CKD in humans has been largely abandoned. Nevertheless, these changes in bone-associated proteins raise the possibility that “ossification”, considered as de novo or altered expression of bone-related proteins in injured renal tubules may occur in CKD.
Matrix Gla Protein (MGP) is a potent inhibitor of ectopic calcification and modulates bone morphogenesis. Little is known about MGP expression or function in kidney.
We investigated renal MGP expression in Sprague-Dawley rats after 5/6 nephrectomy (5/6 Nx) and in human kidney biopsies in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. We analyzed associations between glomerular (n = 182) and tubulointerstitial (TI) (n = 219) MGP mRNA levels and the disease activity/histologic features in NEPTUNE patients. Additionally, uncarboxylated and carboxylated MGP (ucMGP and cMGP, respectively) were localized by immunohistochemistry and quantitated in kidney tissues of patients at different stages of CKD (n = 18).
Renal MGP expression was increased in rats after 5/6 Nx. In NEPTUNE data, baseline estimated glomerular filtration rate (eGFR) negatively correlated with glomerular and TI MGP expression (p <0.001). TI MGP expression strongly correlated with interstitial fibrosis, tubular atrophy, acute tubular injury, and interstitial inflammation, independent of eGFR. Kaplan-Meier analysis and multivariable Cox regression showed that higher levels of TI MGP expression were associated with an increased risk for the composite of 40% decline in eGFR and end-stage renal disease (ESRD) (HR, 3.31; 95% CI, 1.31 to 6.32; p =0.02). Glomerular and tubulointerstitial cells demonstrated nuclear and cytoplasmic cMGP and ucMGP staining, and eGFR inversely correlated with quantified glomerular cMGP staining (p <0.05).
Our data demonstrate that renal MGP expression is increased in human and experimental CKD, and is associated with renal outcome. Additional studies are needed to determine its mechanism of action.
No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease
2013, Kidney International
Citation Excerpt :
There is some laboratory evidence that raises the possibility that disordered phosphorus homeostasis may also contribute to the progression of CKD. In animal models, CKD is associated with intrarenal calcification that is ameliorated with dietary phosphorus restriction.29-32 Furthermore, individuals with proteinuric diabetic kidney disease with renal artery calcification are more likely to progress to ESRD.33
Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m²) from those participating in a community-based screening program were analyzed. Over a median follow-up of 2.3 years, there was no association between quartiles of serum phosphorus and all-cause mortality (adjusted hazards ratio for serum phosphorus over 3.3 to 3.7, over 3.7 to 4.1, and over 4.1 mg/dl, respectively: 1.22 (0.95–1.56), 1.00 (0.76–1.32), and 1.00 (0.75–1.33); reference, serum phosphorus of 3.3 mg/dl and below). Individuals in the highest quartile for serum phosphorus had a significantly higher risk for progression to end-stage renal disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16–10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.
Nutritional Management of Maintenance Hemodialysis Patients
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Trace Elements and Vitamins in Maintenance Dialysis Patients
2003, Advances in Renal Replacement Therapy
Although protein-energy malnutrition occurs commonly in patients with end-stage renal disease undergoing maintenance dialysis treatment, it is not the only form of malnutrition that may exist in these individuals. They may also suffer from deficiencies of micronutrients, particularly trace elements and vitamins. More commonly occurring vitamin deficiencies in maintenance dialysis patients include those for vitamin C (ascorbate), folate, vitamin B6 (pyridoxine), and 1,25-dihydroxycholecalciferol (calcitriol). Among trace elements, deficiencies may occur more commonly for iron, zinc, and possibly selenium, whereas toxicities are more common with aluminum and possibly copper. Evidence suggests that there is an abnormally high prevalence of antioxidant deficiency in maintenance dialysis patients, especially because a low intake of protein and energy may be associated with inadequate ingestion of antioxidant vitamins (ie, vitamins E and C and carotenoids). Thus, some micronutrient deficiencies in maintenance dialysis patients may contribute to the development of atherosclerotic cardiovascular disease. Dietary requirements for vitamins and trace elements in maintenance dialysis patients are reviewed and the recommended daily intakes are discussed.

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^☆: This work was supported by a grant from the Postgraduate Medical Foundation of Australia, the Norman Rose Scholarship of Sydney Hospital, a grant from the Kidney Foundation of the Rocky Mountain Region, the Veterans Administration Hospital General Research Funds and National Institutes of Health Contracts 1-AM-4-2217, CA-15823, AM-17760, AM-18890-01 and NIAMDD Grant AM-26095.

¹: From the Department of Renal Medicine, The Royal North Shore Hospital, St. Leonards, 2065, NSW, Australia.

²: From the Departments of Medicine, Pathology and Surgery, the University of Colorado Medical Center and the Denver Veterans Administration Center, Denver, Colorado.

³: From the Royal Brisbane Hospital, Brisbane, Australia.

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Clinical studyCalcification in end-stage kidneys☆

Abstract

Lancet

Kidney Int

Kidney Int

Kidney Int

Am J Med

Chronic renal disease with secondary hyperparathyroidism

Arch Intern Med

The place of subtotal parathyroidectomy in the management of patients with chronic renal failure

Trans Am Soc Artif Intern Organs

Secondary hyperparathyroidism and renal osteodystrophy in chronic renal failure. Analysis of 195 patients with observations on the effects of chronic dialysis, kidney transplantation and subtotal parathyroidectomy

Medicine (Baltimore)

Soft tissue calcification in chronic dialysis patients

Am J Pathol

Primary hyperparathyroidism. Laboratory and clinical data in 73 cases

JAMA

Vitamin-D intoxication during treatment of hypoparathyroidism

Lancet

Clinical study
Calcification in end-stage kidneys☆