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ABC of kidney disease: How to diagnose- Vascular & Glomerular disease: Dr. NK Hase- Exclusive Masterclass Series Part 2

M3 India Newsdesk Sep 09, 2020

Dr. NK Hase delivers a masterclass on kidney diseases, exclusive in this 4-part weekly series for M3 India. In the second part, he writes about diseases of the vascular and glomerular compartments. You can also drop in your queries at the end of the article. Dr. Hase will address them in a separate article, once this series concludes.


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Vascular compartment

Renal arteries: The most common disease affecting the renal arteries is narrowing of renal artery and is called as Renal Artery Stenosis (RAS).

Clinical presentation: Usually more than 80% stenosis is functionally significant.

  1. Hypertension: It is the most common presentation of renovascular disease.
  2. Ischaemic nephropathy: Haemodynamically significant renal artery stenosis with impaired GFR resulting in chronic renal disease is called as ischaemic nephropathy. It is usually caused by bilateral RAS or single functioning kidney with haemodynamically significant RAS.

When to suspect Renovascular Hypertension?

In the following settings, renovascular hypertension should be strongly suspected:

  1. Onset of hypertension below the age of 30 years without family history of hypertension and obesity.
  2. Severe or resistant hypertension. Resistant hypertension is defined as persistence of hypertension despite concurrent use of adequate doses of three antihypertensive drugs from different classes including diuretics.
  3. Malignant or accelerated hypertension (patient with severe hypertension, papilloedema, retinal haemorrhages, heart failure or kidney failure).
  4. Onset of severe hypertension after the age of 55 years.
  5. Azotemia (increase in serum creatinine) more than 50% within one week of starting ACE inhibitors or ARB.
  6. Recurrent episodes of acute flash pulmonary oedema with ventricular ejection fraction preserved. This is common with bilateral renal artery stenosis.
  7. A systolico-diastolic abdominal bruit lateralised to one side.(sensitivity 40%, specificity 99%). Systolic bruit is more sensitive but less specific.
  8. The presence of diffuse atherosclerosis like peripheral vascular disease, coronary artery disease, cerebrovascular disease with hypertension.
  9. Kidney size difference more than 1.5 cm. A unilateral small kidney (≤9 cm) has 75% association with atherosclerotic RAS.
  10. Absence of pulsation radial, carotid, femoral suggests Takayasu or aortoarteritis in age group less than 40 years.
  11. History of smoking, hypertension, and diffuse atherosclerosis favour atherosclerotic renovascular disease.
  12. Persistent hypokalemia with metabolic alkalosis, with hypertension.

Aetiology of renal artery stenosis

  • Fibromuscular dysplasia (common in young females)
  • Aortoarteritis (young Indians)
  • Atherosclerotic (after age of 55 years, smokers)
  • Vasculitis median size artery involvement (polyarteritis nodosa)
  • Extrinsic lesions compressing renal artery
  • Renal artery embolism

Glomerular compartment

Glomerulus is the filtering unit of the kidney. It is made up of a tuft of specialised capillaries supplied by the afferent arteriole (Figure 1).

Figure 1: Glomerular structure (coronal section)

The entire tuft of the capillaries is covered by the epithelial cells called podocytes. This represents the visceral layer of Bowman’s capsule. At the vascular pole, the visceral layer of Bowman’s capsule transforms into parietal layer which is a simple sqamous epithelium. At the urinary pole, the parietal epithelium abruptly changes into the epithelium of the proximal tubule. The space between the both layers of Bowman’s capsule is called urinary space that opens into the proximal tubular lumen.

The mesangium forms the central region of the glomerulus and provides support to glomerular capillary tuft. The mesangium consists of mesangial cells embedded in an extracellular matrix (ECM). ECM is produced by mesangial cells containing type IV,V collagen, laminin A, B1 and B2, fibronectin, heparin sulfate, and chondroitin sulfate proteoglycans.

Glomerular capillaries are an efficient filter that retain plasma proteins and cellular elements, allowing the free filtration of water electrolytes and other small molecular solutes. The glomerular filtration barrier consists of a fenestrated capillary endothelium with a negatively-charged surface that repels many plasma proteins. Beneath the capillary endothelium is the thick glomerular basement membrane that is also negatively charged. The foot processes of visceral epithelium podocytes form the final barrier. A specialised structure known as slit diaphragm bridge- the filtration slits between adjunct foot processes prevent plasma proteins from leaking into the urinary space (Figure 2).

Figure 2: Glomerular filtration barrier

 

The Glomerular filtration barrier restricts passage of proteins into the urine on the basis of size and charge. The endothelium and GBM are negatively charged, repelling a negative charge protein like albumin. The filtration barrier contains pores restricting molecules with effective molecular radius above 40-450 A.

Cardinal manifestations of Glomerular Injury

  1. Haematuria and proteinuria or both are hallmarks of glomerular injury.
  2. Glomerular haematuria and proteinuria which is predominantly albuminuria is the result of damage to the glomerular filtration barrier.
  3. Acute glomerular injury; may be associated with decreased GFR resulting in oliguria and azotemia.
  4. Salt and water retention resulting in hypertension and oedema.

Characteristics of glomerular haematuria

  1. Haematuria may be visible to the naked eye (called as gross haematuria) or may be detectable only on microscopy (microscopic haematuria).
  2. Gross haematuria occurs at onset in 30 to 50% of children with post-streptococcal GN, IgA nephropathy and thin basement membrane disease.
  3. Glomerular haematuria is present throughout the act of micturition. It is painless without any clots and is smoky, cola, tea, red brown, or rusty in colour.
  4. Microscopic haematuria is present in 100% of patients with acute proliferative GN. Microscopic haematuria on phase contrast microscopy characteristically shows misshapen dysmorphic RBCs. Acanthocytes (ring-shaped RBC with vesicle-shape protrusion) up to 5% (have 50% sensitivity and 95% specificity).
  5. Excreted RBCs are microcytic (MCV <75) and poorly haemoglobinised (decreased MCHC). Presence of RBC cast is hallmark of AGN but present only in 30%.
  6. Haematuria and albuminuria with increase albumin creatinine ratio ≥0.59 has sensitivity of 97% for glomerular haematuria.

Characteristics of non-glomerular haematuria

  • Haematuria originates in the urinary tract, may be painful, bright red to pink in colour. There may be presence of clots
  • Initial haematuria suggests urethral origin, terminal haematuria suggests bladder origin. Haematuria throughout the act of micturition suggests kidney origin
  • Phase contrast microscopy shows isomorphic RBCs with normal size and shape and well haemoglobinised. Proteinuria is absent or just present in traces

Characteristics of glomerular proteinuria

Glomerular proteinuria is due to increase filtration of albumin across the glomerular capillary wall due to loss of electrical charges and increased permeability. This is very sensitive marker of early structural damage/injury to glomeruli. Proteinuria particularly albuminuria more than 2 g is specific for glomerular involvement.

Haematuria with dysmorphic RBC, RBC cast with varying degree of albuminuria suggests proliferative glomerulonephritis (infection-related, post streptococcal GN, IgA nephropathy, ANCA associated vasculitis, Class III and IV lupus nephritis.

Heavy proteinuria with minimal or absent haematuria suggests nonproliferative glomerulopathy (podocytopathy minimal change disease, focal segmental glomerulosclerosis (FSGS) membranous nephropathy, diabetes, amyloidosis).

The normal rate of albumin excretion is less than 30 mg/day (20 mcg/min); persistent albumin excretion between 30 and 300 mg/day (20 to 200 mcg/min) is called moderately increased albuminuria (formerly it was called "microalbuminuria"). Albumin excretion above 300 mg/day (200 mcg/min) is considered to represent severely increased albuminuria (formerly called "macroalbuminuria"). It is also called overt proteinuria, clinical renal disease, or dipstick positive proteinuria.

Proteinuria more than 3.5 g/1.73m2/d is called as ‘’nephrotic range proteinuria” may suggest nephrotic syndrome.

Glomerular proteinuria can be characterised as selective or non-selective based on the ratio of the clearance of IgG to that of albumin or transferrin in the urine (IgG is a γ globulin with MW 150 kD; transferrin is in the β1 band on protein electrophoresis and has MW 88 kD).

C IgG/C albumin or C IgG/C transferrin <0.1 suggests highly selective proteinuria and indicates that the proteinuria is primarily due to defective charge selectivity with intact size selectivity. This is characteristic of steroid responsive childhood minimal change disease (MCD). (C: Stands for clearance)

C IgG/C albumin or C IgG/C transferrin >0.2 suggests non-selective proteinuria. It indicates a significant component of abnormal size selectivity. The non-selective proteinuria is seen in FSGS and other non MCD nephropathies.

Clinical presentation of glomerular injury

Injury to glomeruli results in multiplicity of signs and symptoms of disease. The nature and severity of disease in a given patient is dictated by the nature and severity of glomerular injury. At one end of the spectrum, a patient with mild injury will present with asymptomatic urinary abnormality. At the other end of the spectrum is severe fulminating injury which presents with rapidly progressive renal failure resulting in end-stage kidney disease (Table1).



To read the previous article in this series, click here.

In the next part, Dr. NK Hase will write on diseases affecting the tubulointerstitial compartment.

 

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author Dr. NK Hase is a Director clinical Nephrology & Transplant working at Jupiter Hospital, Thane and former Professor & Head of Department of Nephrology Seth GS Medical College and KEM Hospital, Mumbai.

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