Renal Diseases

What are the three main types of renal disease?

Glomerular, Tubular, and Interstitial.

What is the most common origin of glomerular disorders, and what two mechanisms cause it?

Immune origin is most common; it occurs when immune complexes cause an inflammatory response, OR when antibodies form against glomerular antigens (Ab against glomerular Ag).

What can cause nonimmune-origin glomerular disorders?

Exposure to chemicals/toxins, which causes membrane disruption.

What happens to the membrane's electrical charge in nonimmune glomerular disorders, and what structural change can occur?

The membrane loses its proper electrical charge, and basement membrane thickening can occur.

What can cause amyloid deposition in the glomerulus?

Systemic disorders, such as chronic inflammation.

What is glomerulonephritis, in general terms?

A general, sterile inflammatory process in the glomerulus.

Is glomerulonephritis a single disease, and can it change over time?

No, there are multiple different types/causes, and it may progress from one form to another.

What might the clinical picture of glomerulonephritis include?

Oliguria, edema, azotemia, hypertension, fatigue, and others (variable presentations).

What is the typical urine picture in glomerulonephritis? (what we will see in the sample)

Blood, protein, and casts.

What are the four major/commonly discussed types of glomerulonephritis?

Acute (Post-Streptococcal) Glomerulonephritis, Chronic Glomerulonephritis, IgA Nephropathy, and Nephrotic Syndrome.

What are some of the "other" types of glomerulonephritis listed?

Rapidly Progressive (Crescentic) Glomerulonephritis, Goodpasture Syndrome, Granulomatosis with polyangiitis (formerly Wegener Granulomatosis), Henoch-Schönlein Purpura, Membranous Glomerulonephritis, Membranoproliferative Glomerulonephritis, Minimal Change Disease, and Focal Segmental Glomerulosclerosis.

What infection commonly precedes acute (post-streptococcal) glomerulonephritis?

It commonly occurs after Group A Streptococcus infections

What populations does acute (post-streptococcal) glomerulonephritis typically affect?

Typically affects children and young adults.

What is the underlying mechanism of acute post-streptococcal glomerulonephritis?

Immune complexes deposit on the glomerular membrane, and the resulting inflammatory reaction affects glomerular function.

What is the prognosis for acute post-streptococcal glomerulonephritis?

Usually no permanent kidney damage; 95% recover.

What clinical signs/symptoms may be seen in acute post-streptococcal glomerulonephritis?

Fever, malaise, hypertension, nausea, and edema.

Where might edema appear in acute post-streptococcal glomerulonephritis?

Around the eyes, knees, and ankles. (usually in children)

What is the urine picture in acute post-streptococcal glomerulonephritis?

Oliguria, marked hematuria with dysmorphic RBCs, proteinuria, casts (RBC, hyaline, granular), and WBCs.

What happens to the UA as toxicity resolves, and what may persist longer?

The UA returns to normal as toxicity resolves, but microscopic hematuria may persist until membrane damage resolves.

What other lab results are seen in acute post-streptococcal glomerulonephritis?

Increased ASO titer, positive Anti-DNase B testing (similar to ASO), decreased creatinine clearance, and increased serum creatinine/BUN.

How does chronic glomerulonephritis typically develop, and what does its severity depend on?

It may develop in previously diagnosed glomerular disease, and it depends on the amount of damage to the glomerulus.

What can chronic glomerulonephritis progress to in some cases?

ESRD (End-Stage Renal Disease). (kidneys somtimes just cant keep up anymore)

What is the clinical picture of chronic glomerulonephritis?

Gradually worsening symptoms: fatigue, anemia, hypertension, edema, oliguria, and azotemia.

In some cases: higher BUN or creatinine in serum or plasma (super high) or they might need dialysis or transplant

What is the urine picture in chronic glomerulonephritis?

Hematuria, proteinuria, glucosuria, multiple types of casts (including broad—super-wide ones), and markedly decreased GFR.

What is nephrotic syndrome characterized by?

MASSIVE proteinuria (dumping lots of protein), lipidemia (high lipids in serum/plasma, and so it will be produced in the liver), and pronounced edema.

What is the underlying glomerular change in nephrotic syndrome?

The glomerulus is extremely permeable due to changes in the electrical charge of podocytes affecting filtration.

What causes acute onset nephrotic syndrome?

Circulatory disruption producing systemic shock, which decreases pressure and blood flow to the kidney.

What causes chronic onset nephrotic syndrome?

Progression from other causes of glomerulonephritis.

How does loss of albumin/proteins in nephrotic syndrome lead to increased lipid production?

Loss of albumin and other proteins leads to increased lipid production in the liver.

How does this protein loss ultimately lead to edema?

Lower oncotic pressure in the capillaries increases fluid movement into interstitial spaces, causing edema.

What is the clinical picture of nephrotic syndrome, and what are patients susceptible to?

Edema (eyes, lower extremities); patients are susceptible to infections and clotting problems.

What is the lab picture of nephrotic syndrome?

Decreased serum albumin and hyperlipidemia.

What is the degree of proteinuria seen in nephrotic syndrome?

Marked proteinuria, >3.5 g/day. (will mess up chemistry results)

What other findings make up the urine picture in nephrotic syndrome?

Urinary fat droplets, oval fat bodies, RTEs, epithelial/fatty(bc of excess lipids)/waxy(bc of oliguria) casts, and hematuria.

What glomerular changes occur due to diabetes mellitus?

Thickening of the glomerular membrane, and increased proliferation of mesangial cells with increased deposition of material in the glomerular matrix.

What may these glomerular changes in DM be associated with, and how often do they occur in diabetic patients?

They may be associated with glycosylated proteins due to poor glucose control, and occur in all diabetic patients.

What can DM-related glomerular damage lead to, and how often is renal disease seen?

It may lead to sclerosis; renal disease is frequently seen, with proteinuria in around 55% of patients (ranging from subnephrotic to nephrotic levels).

Slide 14: Tubular Disorders — Overview

What do tubular disorders generally result from?

Disruption of tubular function, due to tubular damage or metabolic/hereditary disorders.

How many tubular functions can be affected, and what is the result?

Single or multiple tubular functions may be affected, resulting in impaired reabsorption or excessive reabsorption.

What does the urine picture in tubular disorders depend on?

It is variable, depending on which function(s) are affected.

Slide 15: Types of Tubular Disorders

What are the tubular disorders covered?

Acute Tubular Necrosis (ATN), Fanconi syndrome, Diabetes insipidus (nephrogenic DI), Renal glucosuria, and Uromodulin-associated kidney disease.

Slide 16: Acute Tubular Necrosis (ATN) — Causes

What does ATN involve damage to, and what is one major category of cause?

Damage to RTEs (renal tubular epithelial cells); one major cause is ischemia (loss of renal blood flow).

What can cause the ischemia leading to ATN?

Shock, physical trauma, sepsis, etc.

What drugs can cause toxin-related ATN?

Antibiotics, anesthetics, radiographic contrast dye, and chemotherapy.

What other toxins (besides drugs) can cause ATN?

Heavy metals, ethylene glycol, hemoglobin (Hgb) or myoglobin (Mgb), and toxic mushrooms.

What is the prognosis for ATN if the initial cause is corrected/removed?

Correction/removal of the initial cause can often result in complete recovery.

Slide 17: Acute Tubular Necrosis — Urine Picture

What is the general urine picture in ATN?

Mild proteinuria, microscopic hematuria, RTEs and RTE casts, and renal cell fragments.

What other casts may be seen in ATN?

Hyaline, granular, waxy, and broad casts.

Slide 18: Fanconi Syndrome — Overview

What does Fanconi syndrome involve in general, and which part of the tubule does it usually affect?

A generalized loss of tubular reabsorption, usually affecting the PCT (proximal convoluted tubule).

What happens to substances that are normally reabsorbed in Fanconi syndrome?

They are lost (not reabsorbed).

Slide 18: Fanconi Syndrome — Causes and Urine Picture

What are the inherited causes of Fanconi syndrome?

Cystinosis and Hartnup disease.

What are the acquired causes of Fanconi syndrome?

Toxins, and complications of renal transplant or plasma cell myeloma.

How does the urine picture in Fanconi syndrome vary, and what is an example finding?

It may vary with the specific substance affected; for example, increased glucose (with a normal blood glucose level) and increased protein.

Slide 19: Diabetes Mellitus vs. Diabetes Insipidus — DM

What is the underlying problem in Diabetes Mellitus (DM)?

The patient does not properly metabolize glucose (an insulin problem).

What are the classic symptoms of DM?

Polyuria, polydipsia, glucosuria, and ketonuria.

What causes glucosuria in DM, and what is the normal renal threshold for glucose?

The renal threshold for glucose has been exceeded; the normal threshold is 160-180 mg/dL.

Slide 19: Diabetes Insipidus (DI)

What is the underlying problem in Diabetes Insipidus (DI)?

No regulation of water absorption (an ADH problem).

What happens to water in DI, and what are the resulting symptoms?

Water isn't reabsorbed, so it is lost, resulting in polyuria and polydipsia.

How can patients with DI stay healthy?

If they can replace the water they're losing.

What are the two types of Diabetes Insipidus?

Neurogenic and Nephrogenic.

What causes Neurogenic DI?

Failure of the hypothalamus to produce ADH.

What causes Nephrogenic DI, and how can it occur?

Inability of the tubules to respond to ADH; it can be inherited or acquired.

Slide 20: DI vs. DM — Comparison

How does Diabetes Insipidus present in terms of urine output, color, glucosuria, and specific gravity (SG)?

Polyuria, pale yellow urine, no glucosuria, and low urine SG.

How does Diabetes Mellitus present in terms of urine output, color, glucosuria, and specific gravity (SG)?

Polyuria, pale yellow urine, glucosuria present, and high urine SG.

Slide 22: Interstitial Disorders — Overview

What is tubulointerstitial disease?

Infections/inflammation causing disorders of the renal interstitium and tubules.

What causes tubulointerstitial disease?

Microorganisms or medications.

Slide 23: Urinary Tract Infections (UTI) — Overview

How common is UTI, and which sex does it affect more?

It is the most common renal disease, and affects females more than males.

What does a Lower UTI involve, and what is it called?

It involves the urethra or bladder, and is called Cystitis.

What does an Upper UTI involve, and what are the two forms?

It involves the renal pelvis, tubules, and interstitium; the two forms are Acute pyelonephritis and Chronic pyelonephritis.

Slide 24: Cystitis — Overview

How frequent is cystitis, and in whom is it more common?

It is the most frequent UTI, and is more frequent in women and children.

What does cystitis affect, and what can happen if it is left untreated?

It is an infection of the bladder; if untreated, it may lead to a more serious upper UTI.

What are the clinical symptoms of cystitis?

Urinary frequency and burning, and lower abdominal pain.

Slide 24: Cystitis — Urine Picture

What are the main urine findings in cystitis?

Many WBCs and bacteria.

What other findings may be seen in cystitis?

Mild proteinuria, hematuria, increased pH, and increased transitional epithelial cells.

Are casts seen in cystitis?

No casts! (NO CASTS)

Slide 25: Acute Pyelonephritis — Overview

What parts of the kidney does acute pyelonephritis (an upper UTI) affect?

The tubules, interstitium, and renal pelvis.

What is the most frequent cause of acute pyelonephritis?

Movement of bacteria from a lower UTI, due to urinary stasis or backward flow.

What conditions can cause the urinary stasis/backward flow leading to acute pyelonephritis?

Pregnancy, reflux back into ureters, and calculi.

What is the prognosis for acute pyelonephritis with treatment?

Antibiotics and removal of the underlying condition(s) may resolve it without permanent damage.

Slide 26: Acute Pyelonephritis — Clinical and Urine Picture

What are the clinical symptoms of acute pyelonephritis?

Urinary frequency, burning, and lower back pain.

What is the urine picture in acute pyelonephritis?

Many WBCs, bacteria, and WBC casts; RTEs may also be seen, along with mild proteinuria and hematuria.

Slide 27: Chronic Pyelonephritis — Overview

What is chronic pyelonephritis?

A chronic infection of the tubules and interstitium.

What can chronic pyelonephritis result in, and what is its most frequent cause?

It may result in permanent damage to the renal tubules; congenital defects producing reflux are the most frequent cause.

Slide 28: Chronic Pyelonephritis — Urine Picture

How does the urine picture in early-stage chronic pyelonephritis compare to acute pyelonephritis?

In early stages, the results are similar to acute pyelonephritis.

What additional findings may appear with progression of chronic pyelonephritis?

Increased protein and blood, and granular, waxy, and broad casts.

Slide 29: Acute Interstitial Nephritis — Overview

What is acute interstitial nephritis?

Inflammation of the renal interstitium and tubules.

What is acute interstitial nephritis usually associated with, and what are some examples?

Usually associated with an allergic reaction to medications, such as antibiotics, NSAIDs, thiazide diuretics, and others.

Slide 29: Acute Interstitial Nephritis — Urine Picture

What is the urine picture in acute interstitial nephritis?

Blood, mild/moderate protein, WBCs, and WBC casts, but NO bacteria.

What additional test may be ordered for acute interstitial nephritis, and what might it show?

Urine eosinophils may be ordered, and may be present.

Slide 31: Renal Failure — Overview

What are the two forms of renal failure, and what does it involve?

May be acute or chronic; involves loss of nephron function due to injury to the glomerulus, tubules, or both.

How much renal mass can be lost before significant symptoms appear?

Can lose more than half of the renal mass before significant symptoms appear.

What are the clinical symptoms of renal failure?

Nausea, vomiting, lethargy, oliguria, decreased GFR, and edema.

Slide 32: Acute Renal Failure (ARF) — Overview

What is Acute Renal Failure (ARF), and is it usually reversible?

A sudden loss of renal function; it is frequently reversible.

What are the primary causes of ARF?

Sudden decreases in blood flow to the kidney, acute glomerular and tubular disease, and renal calculi or tumor obstructions.

Slide 33: Acute Renal Failure — UA Findings

Are UA findings usually diagnostic of ARF itself?

Findings aren't usually diagnostic of ARF, but may help diagnose the underlying cause.

What does the presence of RTEs and casts in ARF suggest about the origin?

Pre-renal or renal origin.

What does the presence of RBCs in ARF suggest?

Glomerular injury.

What do WBC or bacterial casts in ARF suggest about the origin?

Interstitial infection or inflammation of renal origin.

What does the presence of abnormal urothelial cells in ARF suggest?

Malignancy — post-renal origin.

Slide 34: Chronic Renal Failure (CRF) — Overview and Progression

How does Chronic Renal Failure (CRF) often develop?

Often a progression of an original disorder to CRF or ESRD (End-Stage Renal Disease).