Nephrosclerosis, malignant I12.90

The term "malignant nephrosclerosis" was coined by Franz Volhard and Theodor Fahr in 1914 and 1916, respectively. However, both had different opinions regarding the pathogenesis.

Malignant nephrosclerosis was finally accepted as an independent clinical picture by MacMahon in 1968. Von Bohle introduced the clinical and histological subdivision of the malignant form in 1973 (Singh 2000).

Nephrosclerosis is a typical secondary disease of long-term arterial hypertension (Lenz 2008), in which degenerative changes occur in the small and large arterial vessels of the kidney (Thomas 2006).

• Benign nephrosclerosis:

The benign form is mainly associated with histological changes in the media (Keller 2010). It represents the more common form (Lenz 2008).

• Malignant nephrosclerosis:
  • Primary form (this can be caused by hemolytic uremic syndrome [HUS], etc.).
  • secondary form (this is caused by malignant hypertension, scleroderma, etc.) (Lenz 2008).

Malignant nephrosclerosis can develop secondary to malignant hypertension (Herold 2020)

Systemic hypertension leads to permanent damage to the kidneys in about 6% of those affected. In African Americans, hypertensive nephrosclerosis occurs 5 x more frequently than in whites (Kasper 2015).

Nephrosclerosis is the most common cause of renal impairment that occurs with age. The benign form develops from years of hypertension, while the malignant form develops within months or a few years of the onset of hypertension (Lenz 2008).

Benign nephrosclerosis:

The cause of benign nephrosclerosis is long-standing arterial hypertension.

Risk factors are:

• Duration of hypertension
• Race
• older age
• male sex
• pre-existing kidney disease
• low birth weight
• Smoking
• hypercholesterolemia (Kasper 2015)

Malignant nephrosclerosis:

Malignant nephrosclerosis is caused by multiple thrombotic vascular occlusions of the small intrarenal vessels. These may result from:

• massive vessel wall proliferation with stenosis of the vessels
• increased thrombus formation in the intrarenal vessels

Cause of these damages can be:

• postinfection by
  • E. coli
  • HIV
  • Shigella dysenteriae
  • Streptococcus
• medicinal by
  • Quinine
  • cyclosporin A
  • Mitomycin
  • oral contraceptives
  • Tacrolimus
  • Ticlopidine
• secondary by:
  • haemolytic-uraemic syndrome (HUS)
  • malignant hypertension
  • adenocarcinoma
  • bone marrow transplantation
  • organ transplantation
  • scleroderma
  • systemic lupus erythematosus
• other causes:
  • drug abuse (cocaine)
  • genetic
  • idiopathic (Lenz 2008)

Hypertension initially causes vasoconstriction of the afferent vas. As a result of chronic vasoconstriction, hyalinosis of the renal vessels occurs, with ischemia of the glomeruli, sclerosis and interstitial fibrosis. The loss of renal function is protracted over a long period of time (Lenz 2008).

- Malignant nephrosclerosis:

Malignant nephrosclerosis is mainly associated with changes in the intima, especially the subendothelial space (Keller 2010). There is fibrinoid necrosis in the small blood vessels and thrombotic microangiopathy (Kasper 2015). This leads to extreme narrowing of the vascular lumen with rapid loss of filtering function (Keller 2010).

Proteinuria:

The thickening of the intima- walls due to hypertension also causes the vessel walls to stiffen. This leads to the appearance of a pulse wave, the pressure of which is transmitted to the glomerular capillaries and causes microalbuminuria (Segerer 2014).

Clinically, benign nephrosclerosis is asymptomatic. Only through the increasing deterioration of renal function with uremia or concomitant diseases symptoms occur (Lenz 2008).

Patients with nephrosclerosis typically have:

• A long-standing hypertension with secondary damage such as:
  • left ventricular hypertrophy
  • hypertensive ocular background changes
• slowly increasing proteinuria
• inconspicuous sediment
• slowly progressive renal failure (Keller 2010)

Malignant nephrosclerosis

In the malignant form, there are:

• acute deterioration of the general condition (Lenz 2008)
• acute deterioration of renal function under hypertensive derangement (Keller 2010)
• Onset of hypertensive emergency with:
  • chest pain
  • papilledema
  • renal failure (Kasper 2015)

The diagnosis of nephrosclerosis can usually be made by:

• detailed anamnesis
• physical examination
• urinalysis
• serological tests

The diagnosis can only be confirmed by a biopsy. However, this is usually not necessary (Lenz 2008).

An early symptom of nephrosclerosis is microalbuminuria, so that in the case of a suspected nephrosclerosis, this should primarily be sought (Segerer 2014).

Sonography: Sonographically, the kidneys appear small and bumpy (Keller 2010). The parenchymal rim is usually narrowed (Lenz 2008).

Duplex sonography: Duplex sonography of the renal arteries should be performed to differentiate the differential diagnostic diseases (Wolff 2012).

• slowly increasing retention values (Keller 2010).

Since serum creatinine in old age can feign too good renal function with decreasing muscle mass, creatinine clearance should be determined (Lenz 2008).

• mild unselective glomerular (Hofmann 2001) small- and large-molecule proteinuria (Herold 2020) of usually < 1 g / 24 h
• Urine sediment typically unremarkable
• Hyperuricemia (as a sign of reduction in renal blood flow) (Keller 2010).

Hypertensive nephrosclerosis is differentiated into 4 different histological changes:

• 1. preglomerular, vascular changes with
  • Hyaline material is deposited in the intima and / or media by plasma insudation.
  • Medial hypertrophy
• 2. sclerosis of the glomeruli
• 3. atrophy of the tubules
• 4. interstitial fibrosis (Keller 2010)

Hyaline material deposition probably represents the earliest mechanism of damage. This is potentially reversible. Glomerular changes only occur as the disease progresses. (Keller 2010).

Malignant nephrosclerosis is mainly associated with changes in the intima (Keller 2010).

• ischemic kidney disease with
  • Renal artery stenosis
  • athero-embolic events (Keller 2010)
• inflammatory glomerular kidney disease
• interstitial kidney disease (Wolff 2012)

Nephrosclerosis is the second most common cause of chronic renal failure in Germany, accounting for 32% (Glonke 2017).

There is a high concordance on with:

• left ventricular hypertrophy
• hypertensive ocular fundus changes (Wolff 2012).

The first therapeutic goal is to achieve normotensive blood pressure values. It is important to achieve this goal continuously, as there are indications that even short-term increases in pressure lead to a significant and also permanent deterioration in kidney function. It is likely that a reduction in pressure to values < 140 / 90 mmHg is sufficient (Wolff 2012).

If the patient has proteinuria, angiotensin inhibitors should be used (Wolff 2012).

If diabetes mellitus or renal disease is already present, the guidelines recommend a blood pressure setting of < 130 / 80 mmHg (Kasper 2015). To date, no benefit has been demonstrated from lowering < 130 mmHg systolic, even with an eGFR < 20 ml / min / 1.73m2 (Bock 2019).

In the presence of renal disease, antihypertensive treatment is initially by 2 drugs:

• Thiazide diuretic

plus

• ACE inhibitor

However, most patients require a 3rd medication. (Kasper 2015)

In nephrosclerosis with impaired renal function, a cure is usually no longer possible (Lenz 2008).

Although the reduction of high blood pressure slows the progression of proteinuric kidney disease, the therapy does not change the course of hypertensive nephrosclerosis (Kasper 2015). Genetic influences are thought to be the cause here (Keller 2010).

In African Americans, it has been shown that treatment initiated with an ACE inhibitor can slow the deterioration of kidney function - regardless of the effects on blood pressure control (Kasper 2015).

In biopsy-proven patients, 30% developedterminal renal failure within the next 13 years (Segerer 2014).

1. Bock A (2019) Antihypertensive therapy in renal failure: which target values, how to achieve? Therapeutische Umschau Vol. 75 NO.6 Doi:https://doi.org/10.1024/0040-5930/a001010
2. Glonke N (2017) Prospective follow-up study of the effect of RAAS blockade in carriers of Alport syndrome. Inaugural dissertation for the award of the doctoral degree of the Medical Faculty of the Georg-August-University of Göttingen.
3. Herold G et al (2021) Internal Medicine. Herold Verlag 301
4. Hofmann W et al. (2001) Urinary tests for the differentiated diagnosis of proteinuria: known and new information on test strips and urinary proteins. Dtsch Arztebl 98 (12): A - 756 / B - 618 / C - 578
5. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 1630, 1847 - 1848.
6. Keller C K, Geberth S K (2010) Systemic diseases with renal involvement. In: practice of nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-10213-4_9
7. Lenz T et al (2008) Hypertension in clinic and practice. Schattauer Verlag 256 - 258
8. Segerer K et al (2014) Internal medicine modules: kidney and urinary tract. Springer Verlag 101
9. Singh C A (2000) Change in renal function in patients with primary malignant hypertension and secondary malignant nephrosclerosis compared with patients with glomerulonephritis. Dissertation approved by the Medical Faculty of the Rheinisch-Westfälische Technische Hochschule Aachen for the degree of Doctor of Medicine.
10. Thomas C et al. (2006) Histopathology: textbook and atlas on diagnostic findings and differential diagnosis. Schattauer Publishers 191 - 192
11. Wolff T R et al (2012) Internal medicine therapy 2012/2013 - with access to the Elsevier portal. Elsevier Urban und Fischer Verlag 705