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Hypertensive kidney disease is a medical condition referring to damage to the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis (sclerosis referring to the stiffening of renal components). It should be distinguished from renovascular hypertension, which is a form of
secondary hypertension Secondary hypertension (or, less commonly, inessential hypertension) is a type of hypertension which by definition is caused by an identifiable underlying primary cause. It is much less common than the other type, called essential hypertension, ...
, and thus has opposite direction of causation.


Signs and symptoms

Signs and symptoms of chronic kidney disease, including loss of appetite,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...
,
itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
ing, sleepiness or confusion, weight loss, and an unpleasant taste in the mouth, may develop.


Causes

"Hypertensive" refers to high blood pressure and "nephropathy" means damage to the kidney; hence this condition is where chronic high blood pressure causes damages to kidney tissue; this includes the small blood vessels, glomeruli, kidney tubules and interstitial tissues. The tissue hardens and thickens which is known as nephrosclerosis. The narrowing of the blood vessels means less blood is going to the tissue and so less oxygen is reaching the tissue resulting in tissue death (ischemia). Risk factors for HN include poorly controlled, moderate-to-high blood pressure, older age, other kidney disorders, and Afro-Caribbean background, whose exact cause is unclear, as it may be due to either genetic susceptibility or poor health management among people of Afro-Caribbean descent.


Mechanism

In the kidneys, as a result of ''benign
arterial hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
'', hyaline (pink, amorphous, homogeneous material) accumulates in the walls of small arteries and arterioles, producing the thickening of their walls and the narrowing of the arterial openings, a process known as arteriolosclerosis. The resulting inadequate blood flow produces tubular atrophy, interstitial fibrosis, and glomerular alterations (smaller
glomeruli ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...
with different degrees of hyalinization – from mild to sclerosis of glomeruli) and scarring around the glomeruli (periglomerular fibrosis). In advanced stages,
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
will occur. Functional nephrons have dilated tubules, often with hyaline casts in the opening of the tubules. Additional complications often associated with hypertensive nephropathy include glomerular damage resulting in
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
and
blood in the urine Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
. Hypertensive nephropathy refers to kidney failure that can be attributed to a history of hypertension It is a chronic condition and it is a serious risk factor for the development of end-stage kidney disease (ESKD). However, despite the well-known association between hypertension and chronic kidney disease, the underlying mechanism remains unclear. The two proposed mechanisms of HN's pathophysiology both centre around how the glomerulus, a network of dense capillaries that carries out the kidney filtration process, is affected; with one theory identifying glomerular ischemia as the main contributor to HN and the other identifying glomerular hypertension and glomerular hyperfiltration at the centre of HN's pathogenesis.


Glomerular ischemia

High blood pressure in the long term can damage the
endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...
, commonly known as the blood vessel lining. This leads to a build-up of plaques and they can be deposited in the renal arteries causing stenosis and ischemic kidney disease. In this situation, the kidney supplied blood by the narrowed renal artery suffers from inadequate blood flow, which in turn causes the size of the kidneys to decrease. Other consequences include arterial stiffening, which involves a gradual breakdown of elastic fibers and intima (the innermost layer of a blood vessel) thickening.


Glomerular hypertension and glomerular hyperfiltration

An alternative mechanism of hypertensive nephropathy is prolonged glomerular hypertension and hence glomerular hyperfiltration. These can occur simultaneously but not necessarily. The idea is that hypertension results in sclerosis of the glomeruli which ultimately means reduced kidney function. As a compensatory mechanism, the unaffected nephrons (specifically, the preglomerular arterioles) vasodilate to increase blood flow to the kidney perfusion and increase glomerular filtration across undamaged glomeruli.


Diagnosis

Diagnosis of HN is made from clinical history and biochemical investigations. Chronic hypertension with progressive kidney disease progresses over a long period of time. Damage to the glomeruli allows proteins that are usually too large to pass into the
nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
to be filtered. This leads to an elevated concentration of albumin in the urine (albuminuria). This albuminuria usually does not cause symptoms but can be indicative of many kidney disorders. Protein in the urine (proteinuria) is best identified from a 24-hour urine collection. Bilateral renal artery stenosis should always be considered as a differential diagnosis for the presentation of HN. Kidney disease with this etiology can potentially be reversed following vascular intervention.


Histology

In benign nephrosclerosis, the changes occurring are gradual and progressive, however, there can be sufficient kidney reserve capacity to maintain adequate kidney function for many years. The large renal arteries exhibit intimal thickening, medial hypertrophy, duplication of the elastic layer. The changes in small arterioles include hyaline arteriolosclerosis (deposition of hyaline, collagenous material), which causes glomerular collapse (wrinkling and thickening of capillary basement membranes and collapse of capillary lumen) and solidification (glomeruli exhibit sclerosis and increase in mesangial matrix). The degree of scarring correlates with the degree of
glomerular filtration Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
deficit. File:Histopathology of hypertensive glomerular lesion of hypertensive nephropathy.jpg, Light micrograph showing hypertensive glomerular lesion of hypertensive nephropathy: global glomerular collapse and filling of Bowman's space with a lightly staining collagenous material. File:Histopathology of secondary segmental glomerular sclerosis of hypertensive nephropathy.jpg, Light micrograph of glomerulus showing secondary segmental sclerosis of hypertensive nephropathy. File:Histopathology of arcuate artery nephrosclerosis, annotated.jpg, Histopathology of arcuate artery nephrosclerosis, seen as a thickened intima with an onion skin-like architecture. It is presumably a manifestation of hypertensive kidney disease. File:Histopathology of renal interstitial fibrosis of hypertensive nephropathy.jpg, Light micrograph showing signs of hypertensive nephropathy: interstitial fibrosis, tubular atrophy with thickened tubular basement membranes, and fibrous intimal thickening of a small artery (arrow). Malignant nephrosclerosis is where hypertensive nephrosclerosis occurs in presence of
malignant hypertension A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems (especially brain, eyes, heart, aorta, or kidneys). It is different from a hypertensive urgency ...
(when DBP > 130mmHg). Vessels feature intimal thickening,
fibrinoid necrosis Fibrinoid necrosis is a specific pattern of irreversible, uncontrolled cell death that occurs when antigen-antibody complexes are deposited in the walls of blood vessels along with fibrin. It is common in the immune-mediated vasculitides which a ...
, red blood cell fragmentation,
extravasation __NOTOC__ Extravasation is the leakage of a fluid out of its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to th ...
,
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (t ...
. These changes create an exaggerated layered appearance (onion skinning).


Urine test

Microalbuminuria Microalbuminuria is a term to describe a moderate increase in the level of urine albumin. It occurs when the kidney leaks small amounts of albumin into the urine, in other words, when an abnormally high permeability for albumin in the glomerulus ...
(moderate increase in the levels of urinary albumin) is a non-specific finding in patients with vascular disease that is associated with increased risk of cardiovascular events. The majority of patients with benign nephrosclerosis have
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
in the range from 0.5 to 1 g/ 24hr. In the case of glomerular damage occurring in HN,
hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
can occur as well.


Definitive diagnosis

The definitive diagnosis of HN requires morphological examination. Common histological features can be identified in the renal and glomerular vasculature. Glomerulosclerosis is often present, either focally or globally, which is characterized by hardening of the vessel walls. Also, luminal narrowing of the arteries and arterioles of the kidney system. However, this type of procedure is likely to be preceded by a provisional diagnosis based on laboratory investigations.


Future diagnostic approaches

Increasing access to, and use of, genome profiling may provide opportunity for diagnosis based on presentation and genetic risk factors, by identifying ApoL1 gene variants on chromosome 22.


Management

The aim of the medical treatment is to slow the progression of chronic kidney disease by reducing blood pressure and
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
levels. The current published guidelines define ideal BP of <130/80 mmHg for patients with hypertensive nephropathy; studies show that anything higher or lower than this can increase cardiovascular risk. According to the African American Study of Kidney Disease (AASK) trial, after an additional 5 years follow-up upon completion of the 10-year trial, up to 65% of the cohort had progressive nephropathy despite having controlled the mean systolic BP level <135 mmHg.
ACE inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume ...
,
angiotensin receptor blockers Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...
, direct renin inhibitors and aldosterone antagonists, are pharmacological treatments that can be used to lower BP to target levels; hence reducing neuropathy and
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
progression. The management plan should be individualized based on the condition of the patients including comorbidities and previous medical history. In addition, there are lifestyle changes that can be made. Weight reduction, exercise, reducing salt intake can be done to manage hypertensive nephropathy.


Prognosis

According to the United States Renal Data System (USRDS), hypertensive nephropathy accounts for more than one-third of patients on hemodialysis and the annual mortality rate for patients on hemodialysis is 23.3%. Haemodialysis is recommended for patients who progress to end-stage kidney disease (ESKD) and hypertensive nephropathy is the second most common cause of ESKD after diabetes. Patient prognosis is dependent on numerous factors including age, ethnicity, blood pressure and glomerular filtration rate. Changes in lifestyle factors, such as reduced salt intake and increased physical activity have been shown to improve outcomes but are insufficient without pharmacological treatment.


Epidemiology

The incidence of hypertensive nephropathy varies around the world. For instance, it accounts for as many as 25% and 17% of patients starting dialysis for end-stage kidney disease in Italy and France respectively. Contrastingly, Japan and China report only 6 and 7% respectively. Since the year 2000, nephropathy caused by hypertension has increased in incidence by 8.7% In reality, these figures may be even higher, as hypertension is not always reported as the specific cause of kidney disease. It has been recognized that the incidence of hypertensive nephropathy varies with ethnicity. Compared to Caucasians, African Americans in the USA are much more likely to develop hypertensive nephropathy. Of those who do, the proportion who then go on to develop end-stage
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
is 3.5 times higher than in the Caucasian population. In addition to this, African Americans tend to develop hypertensive nephropathy at a younger age than Caucasians (45 to 65, compared to >65).


See also

* Nephropathy


References


Further reading

* *


External links

{{Urologic disease Kidney diseases Hypertension