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Clinical Journal of the American... Dec 2018Patients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. A... (Review)
Review
Patients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. A combination of factors including the innate nephrotoxicity of drugs, underlying patient characteristics that increase their risk for kidney injury, and the metabolism and pathway of excretion by the kidneys of the various agents administered enhance risk for drug-induced nephrotoxicity. This paper will review these clinically relevant aspects of drug-induced nephrotoxicity for the clinical nephrologist.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Kidney; Kidney Diseases; Prescription Drugs
PubMed: 29622670
DOI: 10.2215/CJN.00150118 -
Metabolism: Clinical and Experimental Jun 2022Diabetic kidney disease (DKD) is a devastating microvascular complication associated with diabetes mellitus. Recently, the major focus of glomerular lesions of DKD has... (Review)
Review
Diabetic kidney disease (DKD) is a devastating microvascular complication associated with diabetes mellitus. Recently, the major focus of glomerular lesions of DKD has partly shifted to diabetic tubulopathy because of renal insufficiency and prognosis of patients is closely related to tubular atrophy and interstitial fibrosis. Indeed, the proximal tubule enriching in mitochondria for its high energy demand and dependence on aerobic metabolism has given us pause to focus primarily on the mitochondria-centric view of early diabetic tubulopathy. Multiple studies suggest that diabetes condition directly damages renal tubules, resulting in mitochondria dysfunction, including decreased bioenergetics, overproduction of mitochondrial reactive oxygen species (mtROSs), defective mitophagy and dynamics disturbances, which in turn trigger a series of metabolic abnormalities. However, the precise mechanism underlying mitochondrial dysfunction of renal tubules is still in its infancy. Understanding tubulointerstitial's pathobiology would facilitate the search for new biomarkers of DKD. In this Review, we summarize the current literature and postulate that the potential effects of mitochondrial dysfunction may accelerate initiation of early-stage diabetic tubulopathy, as well as their potential therapeutic strategies.
Topics: Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Kidney Tubules; Kidney Tubules, Proximal; Male; Mitochondria; Reactive Oxygen Species
PubMed: 35358497
DOI: 10.1016/j.metabol.2022.155195 -
Journal of Nippon Medical School =... 2019Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the... (Review)
Review
Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components are constituted by light chain (myeloma) cast nephropathy, light chain associated Fanconi's syndrome (light chain proximal [crystal] tubulopathy), and crystal-storing histiocytosis. In the present review article, we demonstrate the clinicopathological characteristics of MIDD, which is one of the representative diseases of plasma cell dyscrasias, and discuss various renal diseases with the deposition of monoclonal immunoglobulins or their components in glomeruli and the tubulointerstitium. We recommend that these renal diseases are arranged as one disease category, "renal diseases with deposition of monoclonal immunoglobulins or their components", in order to simplify the understanding of complicated diseases in plasma cell dysplasia.
Topics: Antibodies, Monoclonal; Cryoglobulinemia; Fanconi Syndrome; Glomerulonephritis; Histiocytosis; Humans; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Paraproteinemias
PubMed: 30918151
DOI: 10.1272/jnms.JNMS.2019_86-1 -
Journal of the American Society of... Jul 2018Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma... (Review)
Review
Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a "benign" hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.
Topics: Amyloidosis; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Laser Capture Microdissection; Mass Spectrometry; Paraproteinemias; Terminology as Topic
PubMed: 29703839
DOI: 10.1681/ASN.2017121319 -
Indian Journal of Pediatrics Jun 2023Nutritional rickets, caused by vitamin D and/or calcium deficiency is by far the most common cause of rickets. In resource-limited settings, it is therefore not uncommon... (Review)
Review
Nutritional rickets, caused by vitamin D and/or calcium deficiency is by far the most common cause of rickets. In resource-limited settings, it is therefore not uncommon to treat rickets with vitamin D and calcium. If rickets fails to heal and/or if there is a family history of rickets, then refractory rickets should be considered as a differential diagnosis. Chronic low serum phosphate is the pathological hallmark of all forms of rickets as its low concentration in extracellular space leads to the failure of apoptosis of hypertrophic chondrocytes leading to defective mineralisation of the growth plate. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) control serum phosphate concentration by facilitating the excretion of phosphate in the urine through their action on the proximal renal tubules. An increase in PTH, as seen in nutritional rickets and genetic disorders of vitamin D-dependent rickets (VDDRs), leads to chronic low serum phosphate, causing rickets. Genetic conditions leading to an increase in FGF23 concentration cause chronic low serum phosphate concentration and rickets. Genetic conditions and syndromes associated with proximal renal tubulopathies can also lead to chronic low serum phosphate concentration by excess phosphate leak in urine, causing rickets.In this review, authors discuss an approach to the differential diagnosis and management of refractory rickets.
Topics: Humans; Calcium; Fibroblast Growth Factors; Rickets; Vitamin D; Parathyroid Hormone; Vitamins; Phosphates; Familial Hypophosphatemic Rickets
PubMed: 37074534
DOI: 10.1007/s12098-023-04538-4 -
Annual Review of Physiology Feb 2024Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron.... (Review)
Review
Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron. Moreover, mitochondria contribute to cellular health by the regulation of autophagy, (oxidative) stress responses, and apoptosis. Mitochondrial abundance is particularly high in cortical segments, including proximal and distal convoluted tubules. Dysfunction of the mitochondria has been described for tubulopathies such as Fanconi, Gitelman, and Bartter-like syndromes and renal tubular acidosis. In addition, mitochondrial cytopathies often affect renal (tubular) tissues, such as in Kearns-Sayre and Leigh syndromes. Nevertheless, the mechanisms by which mitochondrial dysfunction results in renal tubular diseases are only scarcely being explored. This review provides an overview of mitochondrial dysfunction in the development and progression of kidney tubulopathies. Furthermore, it emphasizes the need for further mechanistic investigations to identify links between mitochondrial function and renal electrolyte reabsorption.
Topics: Humans; Kidney Tubules; Bartter Syndrome; Kearns-Sayre Syndrome; Kidney Diseases; Mitochondria
PubMed: 38012047
DOI: 10.1146/annurev-physiol-042222-025000 -
Journal of the American Society of... Mar 2015Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in...
Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.
Topics: Biopsy; Crystallization; Female; Humans; Kidney; Kidney Diseases; Middle Aged; Multiple Myeloma; Serum Globulins
PubMed: 25190731
DOI: 10.1681/ASN.2014050509 -
Kidney International Reports Aug 2023Lysozyme-associated nephropathy (LyN), a rare cause of kidney injury in patients with chronic myelomonocytic leukemia (CMML), has not been well described to date. We...
INTRODUCTION
Lysozyme-associated nephropathy (LyN), a rare cause of kidney injury in patients with chronic myelomonocytic leukemia (CMML), has not been well described to date. We report the clinicopathologic spectrum of LyN from a multi-institutional series.
METHOD
We identified 37 native kidney biopsies with LyN and retrospectively obtained clinicopathologic data.
RESULTS
Thirty-seven patients had a median age of 74 years and included 78% males. Their most common presentation was acute kidney injury (AKI) or AKI on chronic kidney disease (CKD) (66%) with median estimated glomerular filtration rate (eGFR) of 21.7 ml/min per 1.73 m, and proteinuria of 1.7 g. A minority (15%) had partial Fanconi syndrome. Serum lysozyme levels were elevated in all tested. Hematologic disorder ( = 28, 76%) was the most common etiology, including CMML ( = 15), acute myeloid leukemia ( = 5), and myelodysplastic syndrome (MDS) ( = 5). Nonhematologic causes ( = 5, 14%), included metastatic neuroendocrine carcinoma ( = 3), sarcoidosis, and leprosy. Etiology was unknown in 4 (11%). Pathology showed proximal tubulopathy with abundant hypereosinophilic intracytoplasmic inclusions, with characteristic staining pattern by lysozyme immunostain. Mortality was high (8/30). However, among the 22 alive, including 85% treated, 7 had improved kidney function, including 1 who discontinued dialysis and 6 with increase in eGFR >15 ml/min per 1.73 m compared with eGFR at the time of biopsy.
CONCLUSION
Increased awareness of the full clinicopathologic spectrum of LyN may lead to prompt diagnosis, earlier treatment, and potentially improved outcome of this rare entity.
PubMed: 37547521
DOI: 10.1016/j.ekir.2023.05.007