Test: Nephrotic Syndrome & Nephritic Syndrome and Hematuria - NEET PG MCQ

Membranous nephropathy can be associated with tumors of the colon, lungand hematological malignancies like chronic lymphocytic leukemia.

The occurrence of edema along with reduced urine output suggests a kidney lesion. All three critical diagnostic criteria for nephrotic syndrome are evident: the existence of 3 + proteinuria, serum albumin at the lower end of the normal range, and edema.

Taking into account the patient’s age and maintained kidney function, the diagnosis for this patient is minimal change disease.

• Common primary causes of nephrotic syndrome include kidney conditions such as minimal-change nephropathy, membranous nephropathy, and focal glomerulosclerosis.
• Secondary causes encompass systemic illnesses such as diabetes mellitus, lupus erythematosus, and amyloidosis.

• Key characteristics for diagnosing nephrotic syndrome include:
  • Proteinuria exceeding 3.5 g per 24 hours
  • Hypo-albuminaemia below 2.5 g%
  • Edema, including peri-orbital and pedal edema
• Non-essential features consist of:
  • Hyperlipidaemia, characterised by elevated cholesterol and triglycerides
  • Lipiduria
  • Excretion of protein C, S, or AT III in urine, resulting in a hyper-coagulable state

HIV nephropathy is linked to the onset of focal segmental glomerulosclerosis, which is also observed in reflux nephropathy. Additionally, it is the most prevalent cause of nephrotic syndrome in adults.

In nephrotic syndrome, the intravascular volume is already diminished due to hypoalbuminaemia. When accompanied by diarrhoea and dehydration, there is an additional risk of further reduction in intravascular volume and renal vein thrombosis, which makes the patient more susceptible to acute kidney injury.

• Children with nephrotic syndrome are also at a higher risk for thromboembolic incidents.
• The occurrence of this complication in children ranges from 2% to 5%.
• Both arterial and venous thromboses can occur, such as:
  • renal vein thrombosis
  • pulmonary embolus
  • sagittal sinus thrombosis
  • thrombosis of indwelling arterial and venous catheters

The likelihood of thrombosis is linked to elevated prothrombotic factors (fibrinogen, thrombocytosis, hemoconcentration, and relative immobilisation) and reduced fibrinolytic factors (urinary losses of antithrombin III, proteins C and S).

Renal involvement in leprosy is associated with the level of bacteria, as the kidney serves as the primary organ during splanchic localisation. The most frequent renal complications include:

• Focal segmental glomerulosclerosis (FSGS)
• Mesangioproliferative glomerulonephritis

IgA nephropathy is characterised by the presence of microscopic or gross haematuria, rather than nephrotic syndrome.

In composite forms of glomerular inflammatory reactions, such as membranous glomerulonephritis or diffuse proliferative glomerulonephritis, the loss of size selectivity and possibly also charge selectivity may account for the pattern of non-selective proteinuria observed in these conditions. The primary defect in glomeruli associated with minimal change nephropathy is the loss of charge selectivity in the glomerular capillary wall. As the size selectivity of the glomerular capillary wall remains intact:

• Molecules the size of IgG or larger are excluded,
• while albumin can pass through the small pores, leading to a preferential albuminuria, meaning that the proteinuria is highly selective.

By comparing the clearance of high-molecular-weight proteins to that of albumin, the pattern of glomerular proteinuria can be categorised as either selective or non-selective. The protein commonly utilised as the high-molecular-weight marker is IgG, although other proteins such as haptoglobin, ceruloplasmin, and α₂-macroglobulin (α₂M) have also been employed. Patients with an IgG selectivity index (SI) of 0.2 or above are deemed to have non-selective proteinuria, whereas those with a ratio below 0.2 are classified as having selective proteinuria.

• Infectious diseases include Hepatitis B and C, syphilis, malaria, schistosomiasis, leprosy, and filariasis.
• Cancers encompass colon cancer, lung cancer, breast cancer, renal cancer, esophageal cancer, and neuroblastoma.

Metabolic effects associated with nephrotic syndrome encompass the following:

• Infection
• Hyperlipidaemia and atherosclerosis
• Hypocalcaemia and bone irregularities
• Hypercoagulability
• Hypovolaemia

Although renal vein thrombosis (RVT) has various causes, it is most frequently observed in individuals with nephrotic syndrome (i.e., >3 g/d of protein loss in urine, hypoalbuminaemia, hypercholesterolaemia, and oedema). This syndrome induces a hypercoagulable state. The significant loss of urinary protein is linked to:

• Reduced levels of antithrombin III
• A relative increase in fibrinogen
• Alterations in other clotting factors

All these factors contribute to a higher tendency to develop clots.

Venous thrombosis and pulmonary embolism are recognised complications of nephrotic syndrome. The hypercoagulable state in these instances seems to stem from the loss of anticoagulant proteins in urine, such as antithrombin III and plasminogen, alongside a concurrent rise in clotting factors, particularly factors I, VII, VIII, and X.

• Furthermore, the risk appears to be significantly heightened during the initial 6 months of nephrotic syndrome, reaching nearly 10%.
• This elevated incidence may warrant the routine implementation of preventive anticoagulation therapy during the first half-year of persistent nephrotic syndrome.

Additionally, there is an increased likelihood of arterial thrombotic incidents, including those affecting the coronary and cerebrovascular systems, in individuals with nephrotic syndrome.

• Drugs: Intravenous heroin, analgesics, pamidronate, lithium, anabolic steroids
• Viruses: Hepatitis B, HIV, parvovirus
• Hemodynamic factors - With reduced renal mass:
  • Solitary kidney
  • Renal allograft
  • Renal dysplasia
  • Renal agenesis
  • Oligomeganephronia
  • Segmental hypoplasia
  • Vesicoureteric reflux
• Hemodynamic causes - Without reduced renal mass: Massive obesity, sickle cell nephropathy
• Malignancies: Lymphomas, other malignancies

Henoch schonlein purpura is known as non- thrombocytopenic purpura.
Clinical features of HSP

• Hallmark of HSP is rash, beginning as pinkish maculo-papules which later develop into petechiae or purpura, They present clinically as palpable purpura that evolve From red to purple.
• Arthritis, present In more than 2/3 of children with HSP, Is usually localized to the knees and ankles
• Edema and damage to the vasculature of the gastrointestinal tract may also lead to Intermittent colicky abdominal pain. There may be enlarged mesenteric lymph nodes and hemorrhage Into the bowel.
• Renal involvement occurs In 25-50% of children and may manifest with hematuria, proteinuria, or both; nephritis or nephrosis; or acute renal failure.
• Hepatosplenomegaly and lymphadenopathy
• Neurological Involvement is the development of seizures, paresis, or coma.
• Other rare complications include rheumatoid-llke nodules, cardiac and/or eye involvement, mononeuropathies, pancreatitis, and pulmonary or Intramuscular hemorrhage.

Renal biopsy In P.S.G.N should be considered only in-

1. Presence of acute renal failure
2. Absence of evidence of streptococcal infections or normal complement levels
3. When hematuria and proteinuria leads to diminished renal function
4. Low C3 levels persist more than 2 months

In the first week of symptoms 90% of patients will have a depressed CH50 and decreased levels of C3 with normal levels of C4

• Resolution of the hematuria and proteinuria in the majority of children occurs within 3-6 weeks of the onset of nephritis but 3-10% of children may have persistent microscopic hematuria non nephritic proteinuria or hypertensions
• Serum triglyceride levels are increased in nephrotic syndrome not in nephritis

Renal biopsy In P.S.G.N should be considered only in-

1. Presence of acute renal failure
2. Absence of evidence of streptococcal infections or normal complement levels
3. When hematuria and proteinuria leads to diminished renal function
4. Low C3 levels persist more than 2 months

In the first week of symptoms 90% of patients will have a depressed CH50 and decreased levels of C3 with normal levels of C4

• Resolution of the hematuria and proteinuria in the majority of children occurs within 3-6 weeks of the onset of nephritis but 3-10% of children may have persistent microscopic hematuria non nephritic proteinuria or hypertensions
• Serum triglyceride levels are increased in nephrotic syndrome not in nephritis

• Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of renal function (usually a 50% decline in the glomerular fdtration rate (GFR) within 3 months with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies.
• If left untreated, it rapidly progresses into acute renal failure and death within months.
• In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus, or Wegener granulomatosis; the remaining cases are idiopathic.
• Most types of RPGN are characterized by severe and rapid loss of kidney function featuring severe hematuria, red blood cell casts in the urine, and proteinuria, sometimes exceeding 3 g protein/24 h, a range associated with nephrotic syndrome. Hypertension and edema is also seen. Severe disease is characterized by pronounced oliguria or anuria, which indicates a poor prognosis.
• The clinical picture is consistent with nephritic syndrome, although the degree of proteinuria may occasionally exceed 3 g/24 h, a range associated with nephrotic syndrome

Membranaproliferative Glomerulonephritis

RBC casts indicate glomerular bleeding and are seen with acute glomerulonephritis. Hematuria can be seen with even kidney stones or bladder cancer and hence not a characteristic finding of AGN.

Casts—These urinary sediments are formed by coagulation of albuminous material in the kidney tubules. Casts are cylindrical and vary in diameter Casts in the urine always indicate some form of kidney disorder and should always be reported. If casts are present in large numbers, the urine is almost sure to be positive for albumin.
There are seven types of casts. They are as follows:

• Hyaline casts are the most frequently occurring casts in urine. Hyaline casts can be seen in even the mildest renal disease. They are colorless, homogeneous, transparent, and usually have rounded ends.
• Red cell casts indicate renal hematuria. Red cell casts may appear brown to almost colorless and are usually diagnostic of glomerular disease. White cell casts are present in renal infection and in noninfectious inflammation. The majority of white cells that appear in casts are hyper-segmented neutrophils.
• Granular casts almost always indicate significant renal disease. However, granular casts may be present in the urine for a short time following strenuous exercise. Granular casts that contain fine granules may appear grey or pale yellow in color. Granular casts that contain larger coarse granules are darker. These casts often appear black because of the density of the granules.
• Epithelial casts are rarely seen in urine because renal disease that primarily affects the tubules is infrequent. Epithelial casts may be arranged in parallel rows or haphazardly.
• Waxy casts result from the degeneration of granular casts. Waxy casts have been found in patients with severe chronic renal failure, malignant hypertension, and diabetic disease of the kidney. Waxy casts appear yellow, grey, or colorless. They frequently occur as short, broad casts, with blunt or broken ends, and often have cracked or serrated edges.
• Fatly casts are seen when there is fatty degene-ration of the tubular epithelium, as in degene-rative tubular disease. Fatty casts also result from lupus and toxic renal poisoning. A typical fatty cast contains both large and small fat droplets. The small fat droplets are yellowish- brown in color.
• Broad casts seen in C.K.D.

>5 RBC/μL of centrifuged specimen
There are two cut off for hematuria

• > 3RBC/HPF
• > 5RBC/μL

Nephritic syndrome is characterized by inflammation of the kidney leading to hematuria with hypertension and sub-nephrotic proteinuria.

Sudden onset hypertension in AGN may be associated with LVF, hypertensive encephalopathy and papilledema but not optic neuritis.

• Eighty percent of episodes in IgA nephropathy are associated with upper respiratory tract infections, mainly acute pharyn- gotonsillitis. This synchronous association of pharyngitis and macroscopic hematuria is known as synpharyngitic nephritis.
• Gross hematuria usually appears simultaneously or within the first 48-72 hours after the infection begins; persists less than 3 days; and, in about a third of patients, is accompanied by loin pain, presumably due to renal capsular swelling.
• Urine is usually brown rather than red, and clots are unusual.
• The presenting illness of episodic, grossly visible hematuria is more common in younger people, whereas that of abnormal urine sediment is more frequent in older individuals.

Good pasture syndrome is a rare autoimmune disease in which antibodies attack the lungs and kidneys, leading to bleeding from the lungs and to kidney failure. It may quickly result in permanent lung and kidney damage, often leading to death. It is treated with immuno-suppressant drugs such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood.