Hypertensive nephropathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

• Hypertensive nephropathy is a chronic medical condition, characterized by kidney injury due to long-standing high blood pressure.
• It should be distinguished from “renovascular hypertension“, which is a type of secondary hypertension.
  
  

• In the kidneys, as a result of benign arterial hypertension, hyaline (pink, amorphous, homogeneous material) accumulates in the wall of small arteries and arterioles, leading to thickening of arterial walls and narrowing of the lumens — hyaline arteriolosclerosis. Consequently, tubular atrophy and interstitial fibrosis will occur.
• Glomerular alterations (smaller glomeruli with different degrees of hyalinization – from mild to severe glomerulosclerosis) and podocyte loss can increase the endothelial permeability and filtration of remaining glomerules, leading to microalbuminuria and development of CKD
• Some studies suggest a genetic component in the development of hypertensive nephropathy and nephrosclerosis.
  
  

• The incidence rate for hypertensive kidney disease has been increasing gradually over the past three decades.
• Annually, 25,000 new cases of CKD associated with hypertension, are diagnosed in the US.
• Hypertension is known as the second leading cause of ESRD.
  
  

• Most of the patients with hypertensive nephropathy have no symptoms until kidney failure occurs.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]Nasrin Nikravangolsefid, MD-MPH [3]

Hypertensive nephropathy is classified according to disease severity and histological finding into two subtypes^[1]:

• Benign nephrosclerosis
  • It often occurs in the benign phase of essential hypertension.
  • It is characterized by Hyaline accumulation in the renal arterioles leading to afferent arteriolar narrowing.

• Malignant nephrosclerosis
  • It occurs in the malignant phase of essential hypertension, which is defined by a sudden elevation of blood pressure along with multi-organ damage such as papilledema, central nervous system involvement, cardiac decompensation, and progressive renal failure.
  • It is characterized by fibrinoid necrosis in the afferent arterioles.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2] Nasrin Nikravangolsefid, MD-MPH [3]

• Hypertension can involve any compartment of the kidney ^[1] :
  • Vessels
    • Intimal thickening of small arterioles due to migration of myofibroblasts from media into intimal layer and secretion of collagen which leads to narrowing of the afferent arterioles.
    • thining of media layer and hyalinosis of the afferent arteriole due to loss of smooth muscle cells, which have been changed into myofibroblasts, leads to a reduction in glomerular filtration rate (GFR).
  • Glomerules
    • Constriction of intraglomerular capillaries due to hyalinosis causes glomerular ischemia and reduced filtration which enhances the accumulation of Extracellular Matrix (ECM) in the periglomerular region resulting focal segmental glomerulosclerosis (FSGS) or Global glomerulosclerosis.
    • Hypertrophy of the remaining healthy glomerules maintains filtration but increases intra-glomerular pressure and developing microalbuminuria.
    • Podocyte loss due to hyperfiltration and glomerulosclerosis leads to destroying the filtration barrier and developing proteinuria.
  • Tubulointerestitium
    • Dilatation, flattening and loss of epithelial tubular cells
      • Overexpression of fibrogenic and angiogenic factors such as transforming growth factor b1 (TGF-b1), Endothelin 1 (ET-1), and vascular endothelial growth factor (VEGF) results in disruption of tubular cells junction, transition of epithelial into mesenchymal cells, production of metalloproteinases, cell migration, production of collagen by myofibroblasts in the interstitial and subsequent tubulointerstitial fibrosis.
    • Activation of Renin – Angiotensin – Aldosterone system further contributes to vasoconstriction, cell proliferation, reactive oxygen species production,inducing inflammation and ECM production.
      • Angiotensin II induces differentiation of fibroblasts into myofibroblasts, which synthesize collagen in the periglomerular and peritubular regions.

Changes of kidney compartments induced by Hypertension
Compartment	Changes	Final effects
Vessels	Myofibroblasts migration from media into intimal layer Collagen secretion by myofibroblasts Smooth muscle cells loss in the media layer	Intimal thickening of small arterioles Arteriolar narrowing Thining of media layer Arteriolar hyalinosis
Glomerules	Intraglomerular capillaries constriction Glomerular ischemia Reduced GFR Remained glomerules hypertrophy Podocyte loss	ECM accumulation Glomerulosclerosis, FSGS Increased Intraglomerular pressure Microalbuminuria
Tubulointerestitium	Transition of epithelial into mesenchymal cells Dilatation and loss of epithelial tubular cells Collagen secretion by myofibroblasts RAAS activation	Tubulointerstitial fibrosis Vasoconstriction Inflammation induction ECM accumulation

• Chronic hypoxia hypothesis by Fine et al. in 1998 revealed that hypertension-associated-changes in postglomerular peritubular capillaries cause decrease in blood flow and tubulointerstitial hypoxia, which induce inflammation and epithelial to mesenchymal differentiation. Proximal tubular epithelial cells that are more sensitive to oxygen deficiency than distal cells, are converted into myofibroblasts which produce collagens and inhibit degradation of ECM leading to tubulointerstitial fibrosis. ^[2][3]
• hypoxia also causes up-regulation of fibrogenic and angiogenic factors, which play a major role in fibrosis formation.

• Kidney injury from benign and malignant hypertension results in benign and malignant nephrosclerosis, respectively.

• Benign Nephrosclerosis:
  • The size of the kidneys is reduced or shrunken with loss of cortical mass and fine granularity.
• Malignant nephrosclerosis:
  • Hemorrhages from surface capillaries gives the kidney a “flea-bitten” appearance.

• Benign nephrosclerosis:
  • Afferent arterioles have eosinophilic fibrin deposits in the wall, causing hyaline arteriosclerosis
• Malignant nephrosclerosis:
  • Fibrinoid necrosis in afferent arteriole
  • Hyperplastic arteriosclerosis in inter-lobar arterioles
  • Sclerosis in glomeruli and renal tubules

Figure 1. Fibrous intimal thickening in hypertensive nephropathy

Figure 2. Global glomerular collapse and filling of Bowman’s space with a lightly staining collagenous material

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2], Mehrian Jafarizade, M.D [3]

Renal disease in the hypertensive nephropathy should be diffrentiated from other glomerular diseases.

Glomerular diseases	Disease		History and Symtoms									Laboratory Findings		Pathology
			History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
Acute Nephritic Syndromes	Poststreptococcal Glomerulonephritis[1][2][3]		Streptococcal skin infections Streptococcal pharyngitis 2-3 weeks after infection	Fever Fatigue Skin rash	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	Anti-dsDNA antibodies Anti-C1q antibodies Antineutrophil cytoplasmic antibodies (ANCA)	Hypercellular and inflamed glomeruli	Sub-epithelial immune complex deposits Obliteration of epithelial cell foot processes	Immune complex GN Granular deposit
	Renal disease due to Subacute Bacterial Endocarditis, or cardiac shunt (Atrioventricular)[4][5]		History of infective endocarditis mostly due to S. aureus Cardiac shunt	Fever Fatigue Weight loss	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	ANCA (myeloperoxidase) positive in 1/3 Activation of the alternative complement pathway (Decreased C3, C4) Positive RF Positive anti-GBM autoantibodies	Crescentic GN is the most common pathological features Diffuse membranoproliferative glomerulonephritis features Focal proliferative GN Mesangial proliferative GN	Mesangial deposits, Subendothelial deposits Subepithelial “humps,” in minority of cases	Pauci-immune GN
	Lupus Nephritis[6]		History of SLE features	Lupus criteria: Malar rash Arthritis Arthralgia Anemia Easy bruising	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	Anti-C1q antibodies Anti-dsDNA	Differs based on the disease classification	Differs based on the disease classification	Differs based on the disease classification, mostly immune complex GN Granular deposit
	Antiglomerular Basement Membrane Disease (Goodpasture’s syndrome)[7][8]		Young adults	Dry cough Hemoptysis Malaise  Fever and chills Arthralgia  Fatigue Lethargy Pallor Anorexia Easy bruising	+	+	+	+	+	+	–	–	ANCA (myeloperoxidase) Positive anti-GBM autoantibodies	Hypercellular and inflamed glomeruli (Crescent formation)	Diffuse thickening of the glomerular basement membrane with absence of sub-epithelial and sub-endothelial deposits	Immune complex GN Linear deposit
	IgA Nephropathy[9][10]		Young children History of mucosal infections (e.g. gastroenteritis) and upper respiratory tract infection 2-3 days after infection (synpharyngitic)	Low grade fever Flank pain	+	+/-	+	+/-	+	–	+	–	Immune complex deposition	Crescent formation	Mesangial proliferation	Immune complex GN, granular deposite
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	ANCA Small-Vessel Vasculitis[11][12]	Granulomatosis with Polyangiitis (Wegener’s)[13][14][15]	Middle age male	Constitutional symptoms Dyspnea Purpura Arthralgias Neurologic dysfunction Sinusitis Otitis media Epistaxis.	+	+	+	+/-	+	–	+	–	ANCA	Necrotizing and crescentic glomerulonephritis	Subendothelial edema Microthrombosis Degranulation of neutrophils	Pauci-immune GN
		Microscopic Polyangiitis[16]	+/-	Constitutional symptoms Dyspnea Purpura Arthralgias Neurologic dysfunction	+	+	+	+	+	+		–	P-ANCA	Hypercellular and inflamed glomeruli (Crescent formation)	Hypercellular and inflamed glomeruli (Crescent formation)	Pauci-immune GN
		Churg-Strauss Syndrome[17]	+/-	Asthma Sinusitis Myalgia  Arthralgia Purpura Arrythmias Peripheral neuropathy	+	+	+	+	+	+		–	C-ANCA	Hypercellular and inflamed glomeruli (Crescent formation)	Hypercellular and inflamed glomeruli (Crescent formation)	Pauci-immune GN
	Membranoproliferative Glomerulonephritis[18][19]		Idiopathic Hepatitis B and C (Type 1) C3 nepritic factor (Type2)	Hematuria Oliguria Periorbital edema Hypertension	+	+	+	+/-	+	+	–	–	–	Thick glomerular basement membrane (Tram-track appearance)	Mesangial proliferation Leukocyte infiltration	Immune complex GN Granular deposite
	Henoch-Schönlein purpura [20]		Most common in young male, following upper respiratory infections	Skin manifestations- Palpable purpura on buttocks Gastrointestinal manifestations- Abdominal pain Melena Bloody diarrhea Hematemesis Joints manifestations- Arthralgia	+	+	+	+/-	+	+	–	–	–	Diffuse mesangial IgA deposits often associated with mesangial hypercellularity	Diffuse mesangial IgA deposits often associated with mesangial hypercellularity	Immune complex GN, granular deposite
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Cryoglobulinemia[21]		Patients having cryoglobulinemia may have positive history of: Hepatitis C infection Hepatitis B infection Leg ulcers Recurrent thrombosis	Pulmonary symptoms: Difficulty breathing Cough Cutaneous symptoms: Purpura  Skin ulcer Gastrointestinal symptoms: Abdominal pain General symptoms: Fever Arthralgia, Myalgia Fatigue Blurring/loss of vision Diplopia Confusion	+/-	+	+/-	+	+/-	+/-	+/-	+/-	+/-	Membranoproliferative glomerulonephritis	Mesangial and subendothelial deposits	Prominent IgM and C3
Nephrotic Syndrome	Minimal Change Disease[22][23]		Young children Recent infection and immunization Atopy Hodgkin lymphoma Thrombosis (due to urinary loss of antithrombin-III)		–	+	–	+	+/-	+	–	+		Normal	Fusion of podocytes	–
	Focal Segmental Glomerulosclerosis[24][25][26]		Idiopathic HIV Heroine use Sickle cell disease Interferon Severe obesity Mixed cryoglobulinemia (Hepatitis C)		–	+	–	+	+/-	+	–	+		Focal (some glomeruli) and segmental (only part of glomerulus)	Effacement of podocytes	–
	Membranous Glomerulonephritis[27][28]		Idiopathic Hepatitis B and C Solid tumors Systemic lupus erythematosus Drugs (NSAIDS, pencilamine, gold, captopril)		–	+	–	+	+/-	+	–	+	Immune complex deposition	Thick glomerular basement membrane	Sub-epithelial immune complex depositis with ‘spike and dome’ appearance	Immune complex GN, granular deposite
	Diabetic Nephropathy[29][30][31][32][33][34][35][36][37][38]		For more information on diabetes click here.		–	+	–	+	+/-	+	–	+		Diffuse mesangial matrix expansion (nodular glomerulosclerosis) Increased mesangial hypercellularity Prominent glomerular basement membranes Thick basement membrane without any deposit	Nodular glomerulosclerosis	–
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Glomerular Deposition Diseases	Light Chain Deposition Disease[39]	Occurs in the setting of high tumor burden	–	–	+	–	+	+/-	+	–	+	–	Light-chain deposits	Granular deposits on electron microscopy	Detection of light chain deposits using anti–light chain antibody
		Renal Amyloidosis[40][41][42][43]	For the secondary causes of amloidosis: Tuberculosis Familial Mediterranean fever Rheumatoid arthritis Multiple myeloma	Dyspnea Lethargy Weight loss Bleeding tendency	–	+	–	+	+/-	+	–	+	–	Diffuse glomerular deposition of amorphous hyaline material (nodular pattern), in mesangium (weakly staining with periodic acid-Schiff (PAS)	Nodular deposit	AA amyloidosis type: negative for immunoglobulins and complement AL amyloidosis type: Positive for lambda or kappa light chains
		Fibrillary-Immunotactoid Glomerulopathy[44]	Malignancy Monoclonal gammopathy Autoimmune disease	–	+/-	+	+/-	+/-	+/-	+	+/-	+/-	–	Diffuse sclerosing glomerulonephritis Diffuse proliferative glomerulonephritis Membranoproliferative glomerulonephritis Mesangioproliferative/sclerosing disease Membranous glomerulonephritis	Large fibrillar deposits in the mesangium randomly Glomerular capillary walls different from amloidosis No staining with Congo red or thioflavine-T or with antibodies to a specific type	Positive for immunoglobulin G (IgG), C3 Kappa and lambda (ie, polyclonal) light chains
		Fabry’s Disease[45][46][47]	Family history suggestive of the disorder	Anhidrosis or decreased sweating Fatigue Angiokeratomas Burning pain of the extremities Corneal opacities. Dysphagia Abdominal pain Steatorrhea Delayed puberty Raynaud’s phenomenon Hearing loss Telangiectasis Ataxia	–	+	–	+	+/-	+	–	+	–	Vacuolization of visceral glomerular epithelial cells (podocytes) and distal tubular epithelial cells Glycolipid accumulation	Myeloid or zebra bodies: Gb3 deposition within enlarged secondary lysosomes as lamellated membrane structures Inclusions, composed of concentric layers (onion skin appearance)	–
Basement Membrane Syndrome	Alport’s Syndrome[48][49][50][51][52][53]		Positive family history	Auditary: Early Tinnitus Vertigo High-frequency progressive bilateral hearing loss Occular problems: Refractory Error Arcus Glaucoma Band Keratopathy Lenticonus Spherophakia Cataracts	–	+	–	+	+/-	+	–	+	–	Early stage: unremarkable Late stages: glomerulosclerosis, interstitial fibrosis, and interstitial foam cells (due to prolonged proteinuria).	Within glomerular basement membrane (GBM): longitudinal splitting of the lamina densa	Absence of staining of the alpha-3, alpha-4, and alpha-5 (IV) chains in the glomerular basement membrane Minimal binding to a glomerulus in indirect immunofluorescence microscopy with anti-glomerular basement membrane antibodies
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Thin Basement Membrane Disease[54][55]		Positive family history Gross hematuria following upper respiratory tract infection	–	–	+	-/+	–	-/+	–	-/+	–	–	–	Diffuse thinning of the glomerular basement membranes (GBM)	–
	Nail-Patella Syndrome[56][57]		Positive family history	Poorly developed fingernails, toe nails, and patellae (kneecaps). Elbow deformities Abnormally shaped pelvis bone (hip bone) Knee may be small, deformed or absent	+	+	–	–	–	–	–	–	–	Mostly unremarkable changes Secondary FSGS Late stages: Global glomerulosclerosis, Tubulointerstitial fibrosis	Glomerular basement membranes (GBMs): Focal or diffuse irregular thickening with electron-lucent areas (moth-eaten appearance) containing type III collagen bundles. Similar collagen fibrils can be seen in mesangial matrix. Podocytes: Segmental effacement of foot processes.	Immunofluorescence studies are typically negative. Nonspecific IgM and C3 deposition may be seen in sclerotic glomeruli.
Glomerular-Vascular Syndromes	Hypertensive Nephrosclerosis[58]		Chronic hypertension	Hypertensive retinal changes. High jugular venous pressure Rales from pulmonary edema on auscultation .Signs of left ventricular hypertrophy Left ventricular heave Shifting of apex towards the left S3 and gallop rhythm Loud S2 Ascites Paralysis from stroke secondary to hypertension Inferior limb edema	+/-	+/-	+	+/-	+/-	+/-	–	+/-	–	Interstitial fibrosis and atrophy Medial thickening and intimal fibrosis of medium-sized and larger vessels Arteriolar thickening, and hyalinosis Chronic stages: Global sclerosis Focal segmental sclerosis
	Cholesterol Emboli[59]		Atherosclerotic cardiovascular disease Anticoagulation therapy Cardiopulmonary resuscitation Hypertension Aortic aneurysm Hypercholesterolemia Smoking history Male sex Age over 55 years Vascular procedures Invasive angiography Aortic aneurysm rupture or surgery Vascular surgery	Depends on the organ involved	+/-	+/-	+	+/-	+/-	+/-	–	+/-	–	Atheroemboli are seen in interlobular and arcuate arteries, as lance-shaped clefts, due to dissolution of cholesterol crystals Acute lesions: Atheroemboli are surrounded by red blood cells, fibrin, and leukocytes, with multinucleated giant cell reactions Chronic lesions: Cholesterol clefts are surrounded by intimal fibrosis Vessel recanalization of chronic lesions can occur. Global and segmental sclerosis of glomeruli may be present.	Extensive foot process effacement can be seen	Not specific changes
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Sickle Cell Disease[60]		Positive family history	Pain and/or bone pain Dactylitis Blurry vision Persistent and painful erection Numbness Tingling Motor skill loss Speech deficits Gait disturbance Leg ulceration Jaundice	+/-	+/-	+/-	–	–	–	–	–	–	Glomerular hypertrophy Hemosiderin deposits Focal areas of hemorrhage or necrosis Chronic stage: interstitial inflammation, edema, fibrosis, tubular atrophy, and papillary infarcts Glomerular enlargement and focal segmental glomerulosclerosis (FSGS)
	Thrombotic Microangiopathies[61]		Click for more information on Thrombotic Microangiopathies.		+	+/-	+	+/-	+/-	+/-	–	–	–	Acute stage: Inravasculr fibrin thrombi Chronic stage: Endocapillary hypercellularity. Intimal proliferation of arterioles	Swollen glomerular endothelial cells with loss of fenestrations Chronic stage: interposed cells with new GBM matrix material deposition.	Thrombi stain positive for fibrinogen
	Antiphospholipid Antibody Syndrome [62][63][64]		Thrombosis Miscarriage  History of nephropathy History of hematologic abnormalities Nonthrombotic neurologic symptoms, such as migraine headaches Pulmonary hypertension	Fatigue Fever Weight loss Venous thrombosis Arterial thrombosis Thrombocytopenia Recurrent fetal loss	+	+/-	+	+/-	+/-	+/-	–	–	–	Acute stage: Inravasculr fibrin thrombi Chronic stage: Endocapillary hypercellularity. Intimal proliferation of arterioles	Swollen glomerular endothelial cells with loss of fenestrations Chronic stage: interposed cells with new GBM matrix material deposition.	Thrombi stain positive for fibrinogen

Some infectious diseases such as HIV, HBV, HCV, syphilis, leprosy, malaria, and schistosomiasis may cause glomerular diseases.

References

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22. ↑ Saha TC, Singh H (November 2006). “Minimal change disease: a review”. South. Med. J. 99 (11): 1264–70. doi:10.1097/01.smj.0000243183.87381.c2. PMID 17195422.
23. ↑ Saleem MA, Kobayashi Y (2016). “Cell biology and genetics of minimal change disease”. F1000Res. 5. doi:10.12688/f1000research.7300.1. PMC 4821284. PMID 27092244.
24. ↑ Rosenberg AZ, Kopp JB (March 2017). “Focal Segmental Glomerulosclerosis”. Clin J Am Soc Nephrol. 12 (3): 502–517. doi:10.2215/CJN.05960616. PMC 5338705. PMID 28242845.
25. ↑ Jefferson JA, Shankland SJ (September 2014). “The pathogenesis of focal segmental glomerulosclerosis”. Adv Chronic Kidney Dis. 21 (5): 408–16. doi:10.1053/j.ackd.2014.05.009. PMC 4149756. PMID 25168829.
26. ↑ Gephardt GN, Tubbs RR, Popowniak KL, McMahon JT (October 1986). “Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens”. Arch. Pathol. Lab. Med. 110 (10): 902–5. PMID 2429634.
27. ↑ Lai WL, Yeh TH, Chen PM, Chan CK, Chiang WC, Chen YM, Wu KD, Tsai TJ (February 2015). “Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment”. J. Formos. Med. Assoc. 114 (2): 102–11. doi:10.1016/j.jfma.2014.11.002. PMID 25558821.
28. ↑ Wasserstein AG (April 1997). “Membranous glomerulonephritis”. J. Am. Soc. Nephrol. 8 (4): 664–74. PMID 10495797.
29. ↑ Drummond K, Mauer M, International Diabetic Nephropathy Study Group (2002). “The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes”. Diabetes. 51 (5): 1580–7. PMID 11978659.CS1 maint: Multiple names: authors list (link)
30. ↑ Hørlyck A, Gundersen HJ, Osterby R (1986). “The cortical distribution pattern of diabetic glomerulopathy”. Diabetologia. 29 (3): 146–50. PMID 3699305.CS1 maint: Multiple names: authors list (link)
31. ↑ Alpers CE, Hudkins KL (2011). “Mouse models of diabetic nephropathy”. Curr Opin Nephrol Hypertens. 20 (3): 278–84. doi:10.1097/MNH.0b013e3283451901. PMC 3658822. PMID 21422926.CS1 maint: PMC format (link)
32. ↑ Kimmelstiel P, Wilson C (1936). “Intercapillary Lesions in the Glomeruli of the Kidney”. Am J Pathol. 12 (1): 83–98.7. PMC 1911022. PMID 19970254.CS1 maint: PMC format (link)
33. ↑ Alpers CE, Biava CG (1989). “Idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity”. Clin Nephrol. 32 (2): 68–74. PMID 2766585.
34. ↑ Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M (2007). “Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy”. Diabetes. 56 (8): 2155–60. doi:10.2337/db07-0019. PMID 17536064.CS1 maint: Multiple names: authors list (link)
35. ↑ Najafian B, Crosson JT, Kim Y, Mauer M (2006). “Glomerulotubular junction abnormalities are associated with proteinuria in type 1 diabetes”. J Am Soc Nephrol. 17 (4 Suppl 2): S53–60. doi:10.1681/ASN.2005121342. PMID 16565248.CS1 maint: Multiple names: authors list (link)
36. ↑ Najafian B, Kim Y, Crosson JT, Mauer M (2003). “Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy”. J Am Soc Nephrol. 14 (4): 908–17. PMID 12660325.CS1 maint: Multiple names: authors list (link)
37. ↑ Najafian B, Alpers CE, Fogo AB (2011). “Pathology of human diabetic nephropathy”. Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.CS1 maint: Multiple names: authors list (link)
38. ↑ Najafian B, Alpers CE, Fogo AB (2011). “Pathology of human diabetic nephropathy”. Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.CS1 maint: Multiple names: authors list (link)
39. ↑ Hutchison CA, Cockwell P, Stringer S, Bradwell A, Cook M, Gertz MA, Dispenzieri A, Winters JL, Kumar S, Rajkumar SV, Kyle RA, Leung N (June 2011). “Early reduction of serum-free light chains associates with renal recovery in myeloma kidney”. J. Am. Soc. Nephrol. 22 (6): 1129–36. doi:10.1681/ASN.2010080857. PMC 3103732. PMID 21511832.
40. ↑ Baker KR, Rice L (2012). “The amyloidoses: clinical features, diagnosis and treatment”. Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
41. ↑ Gillmore JD, Hawkins PN (October 2013). “Pathophysiology and treatment of systemic amyloidosis”. Nat Rev Nephrol. 9 (10): 574–86. doi:10.1038/nrneph.2013.171. PMID 23979488.
42. ↑ Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). “Primary systemic amyloidosis as a real diagnostic challenge – case study”. Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
43. ↑ Pepys MB (2006). “Amyloidosis”. Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
44. ↑ Korbet SM, Schwartz MM, Lewis EJ (March 1991). “Immunotactoid glomerulopathy”. Am. J. Kidney Dis. 17 (3): 247–57. PMID 1996564.
45. ↑ Alroy J, Sabnis S, Kopp JB (June 2002). “Renal pathology in Fabry disease”. J. Am. Soc. Nephrol. 13 Suppl 2: S134–8. PMID 12068025.
46. ↑ Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999). “Prevalence of lysosomal storage disorders”. JAMA : the Journal of the American Medical Association. 281 (3): 249–54. PMID 9918480. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
47. ↑ Branton MH, Schiffmann R, Sabnis SG; et al. (2002). “Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course”. Medicine. 81 (2): 122–38. PMID 11889412. Unknown parameter |month= ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
48. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
49. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
50. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
51. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
52. ↑ Amari F, Segawa K, Ando F (1994). “Lens coloboma and Alport-like glomerulonephritis”. Eur J Ophthalmol. 4 (3): 181–3. PMID 7819734.CS1 maint: Multiple names: authors list (link)
53. ↑ Govan JA (1983). “Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes?”. Br J Ophthalmol. 67 (8): 493–503. PMC 1040106. PMID 6871140.CS1 maint: PMC format (link)
54. ↑ Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang YY (2003). “Thin basement membrane nephropathy”. Kidney Int. 64 (4): 1169–78. doi:10.1046/j.1523-1755.2003.00234.x. PMID 12969134. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
55. ↑ Hou P, Chen Y, Ding J, Li G, Zhang H (2007). “A novel mutation of COL4A3 presents a different contribution to Alport syndrome and thin basement membrane nephropathy”. Am. J. Nephrol. 27 (5): 538–44. doi:10.1159/000107666. PMID 17726307.CS1 maint: Multiple names: authors list (link)
56. ↑ Najafian B, Smith K, Lusco MA, Alpers CE, Fogo AB (October 2017). “AJKD Atlas of Renal Pathology: Nail-Patella Syndrome-Associated Nephropathy”. Am. J. Kidney Dis. 70 (4): e19–e20. doi:10.1053/j.ajkd.2017.08.001. PMID 28941488.
57. ↑ Guidera KJ, Satterwhite Y, Ogden JA, Pugh L, Ganey T (1991). “Nail patella syndrome: a review of 44 orthopaedic patients”. J Pediatr Orthop. 11 (6): 737–42. PMID 1960197.
58. ↑ Hughson MD, Puelles VG, Hoy WE, Douglas-Denton RN, Mott SA, Bertram JF (July 2014). “Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race”. Nephrol. Dial. Transplant. 29 (7): 1399–409. doi:10.1093/ndt/gft480. PMC 4071048. PMID 24327566.
59. ↑ Lusco MA, Najafian B, Alpers CE, Fogo AB (April 2016). “AJKD Atlas of Renal Pathology: Cholesterol Emboli”. Am. J. Kidney Dis. 67 (4): e23–4. doi:10.1053/j.ajkd.2016.02.034. PMID 27012950.
60. ↑ Wesson DE (June 2002). “The initiation and progression of sickle cell nephropathy”. Kidney Int. 61 (6): 2277–86. doi:10.1046/j.1523-1755.2002.00363.x. PMID 12028473.
61. ↑ Lusco MA, Fogo AB, Najafian B, Alpers CE (December 2016). “AJKD Atlas of Renal Pathology: Thrombotic Microangiopathy”. Am. J. Kidney Dis. 68 (6): e33–e34. doi:10.1053/j.ajkd.2016.10.006. PMID 27884283.
62. ↑ Jayakody Arachchillage D, Greaves M (2014). “The chequered history of the antiphospholipid syndrome”. Br J Haematol. 165 (5): 609–17. doi:10.1111/bjh.12848. PMID 24684307.
63. ↑ Jayakody Arachchillage D, Greaves M (2014). “The chequered history of the antiphospholipid syndrome”. Br J Haematol. 165 (5): 609–17. doi:10.1111/bjh.12848. PMID 24684307.
64. ↑ Popa A, Voinea L, Pop M, Stana D, Dascalu AM, Alexandrescu C; et al. (2008). “[Primary antiphospholipid syndrome]”. Oftalmologia. 52 (1): 13–7. PMID 18714484.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]Nasrin Nikravangolsefid, MD-MPH [3]

The incident counts and adjusted rates for hypertensive renal disease has been increasing gradually over the past three decades. 25,000 new cases of chronic renal failure attributable to high blood pressure, are diagnosed every year in the US. It has also contributed significantly to the increase in the number of patients undergoing dialysis from renal insufficiency.

• More than 20% of patients with systemic hypertension have chronic renal insufficiency.
• The prevalence of hypertensive nephropathy among those with hypertension is 24.6%.
• According to USRDS annual data report“USRDS”., the overall prevalence of CKD among patients aged greater than 65 years in 2017 was 14.5% (186,997 from 1,291,640), however in the hypertensive population aged 65+ years was 16.3%.
• Incidence of hemodialysis, peritoneal dialysis, and transplantation among CKD due to hypertension in the US population was reported 35,843 from 124,369 in 2017. Whereas, the prevalence of these therapeutic modalities was 192,907 from 743,624.

• Hypertensive renal disease has a higher prevalence in those aged 65 years and older.
• The prevalence of CKD due to hypertension increased with age from 11.7% at ages 65–74 to 25.5% at age≥ 85.

• The prevalence of hypertensive nephropathy is higher in African Americans.

• http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5608a2.htm

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]Nasrin Nikravangolsefid, MD-MPH [3]

• High systolic blood pressure is a very strong risk factor for the development of hypertensive nephrosclerosis.
• African Americans are more likely to develop hypertensive nephropathy. Firstly, a number of causes had been suggested:
  • Higher prevalence and severity of hypertension
  • Lower socioeconomic status
  • Poor healthcare accessibility.
• However, Ethnic differences related to hypertensive nephropathy remained after adjusting age, sex, and prevalence of hypertension among ethnic groups, suggesting the presence of genetic predisposition in this population.^[1]

• Genetic susceptibility
  • Non-muscle myosin heavy chain 9 gene (MYH9), which regulates the function of podocyte cytoskeleton, is associated with hypertensive ESRD in African Americans.^[2]
  • Solidified glomerulosclerosis secondary to hypertension in African American is associated with apolipoprotein L1 gene (APOL1)^[3]
  • Chromogranin A gene variants, which block secretion of catecholamine, is also contributed to hypertensive ESRD in African Americans.^[4]

• The Framingham heart study showed that a combination of hypertension with a mild reduction in glomerular filtration rate increases the risk of developing chronic renal failure.

• Diabetes, smoking, obesity and high levels of low density lipoproteins also accelerates the progression of renal damage secondary to hypertension.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

• Microalbuminuria (less than 300 mg/ dl) is the first sign of renal damage secondary to hypertension.
• It is widely used as a screening technique to detect renal damage at an early stage.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

• Chronic renal failure leading to dialysis
• Congestive heart failure
• Stroke
• CAD
• Insulin resistance
• Hyperuricemia causing symptoms of gout
• Peripheral artery disease

• Uncontrolled hypertension can accelerate the progression of renal damage secondary to hypertension, eventually causing end stage renal disease, requiring dialysis or renal transplant.

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