GLOMERULONEPHRITIS

NephrItic Syndrome: MInor. Hematuria, proteinuria < 3.5g/24 hrs, possible HTN & edema

NephrOtic Syndrome: MajOr. Hematuria, proteinuria > 3.5 g / 24 hrs, HTN, edema,
Hyopalbuminea, Hyperlipidemia, Lipiduria

 Complications of nephrotic syndrome: clotting, low vitamin D, low iron, infections

 Secondary Causes of Nephrotic Syndrome: Systemic disorders extrinsic to kidney that affects other organs in
addition to kidney i.e; DM, SLE, Amyloidosis, HIV, Hepatitis, Sarcoidosis, Sickle cell disease, HUS/TTP, tumors,
post-infections, post-strept, Goodpasture’s syndrome, vasculitis, alport’s syndrome

 Primary Causes of Nephrotic Syndrome: (idiopathic) confined to the kidney. i.e; minimal change disease, focal
segmental glomerulosclerosis (FSGS), membranous nephropathy

SECONDARY
DM: MC cause of ESRD in US, sugar binding to protein thickens the glomerulus and blood vessels (mainly the
efferent aa) (GBM thickening, sclerosis) → increases pressure in the glomerulus, Sx: initial increase in GFR leading to
polyuria, microalbuminuria, proteinuria; → eventually decrease as GFR decreases, Tx: BP and glucose controlim

SLE: immune complexes deposit in the kidneys and initiate an inflammatory reaction, Staging: I - normal, II -
mesangial (A - normal light, mesangial deposits, B - mesangial hypercellularity), III - focal proliferative, IV - diffuse
proliferative, V - membranous, Tx: corticosteroids for the SLE

Amyloidosis: Deposition of Light chains

HIV: ARI: d/t dehydration &/ meds. CRI: d/t other co-existing dz. HIV nephropathy. AA. maj proteinuria, rapid →
ESRD. Glomerular lesion=collapsing FSGS (focal segmental glomerulosclerosis), proliferation.

Hepatitis B: Associated w/ membranous nephropathy, autoAbs target the GBM & it thickens

Hepatitis C: Associated w/ MPGN & cryoglobulins → glomerular thickening d/t complement system activation

Sarcoidosis: usually clinically silent. Don’t see tubule/bowmans bc everything scarred down.

Sickle Cell Disease: May develop papillary necrosis & FSGS. Glomerulus scarred down = not doing job.

HUS/TTP: complication of enterohemorrhagic E. coli, Patho: multiple intracapillary glomerular thrombi may also be
associated with drugs [cyclosporin, tacrolimus, mitomycin], Sx: bloody diarrhea Dx: Peripheral blood smear = helmet
cells, spherocytes, large plt, marked red cell fragmentation aka microangiopathic hemolytic anemia
(thrombocytopenia).

Tumors: liquid tumors → minimal change disease, solid tumors → membranous nephropathy, MPGN
Post infectious/infections: post-strept GN about 2 wks following group A beta hemolytic strept infxn = dec C3.
Glomeruli = enlarged & hypercellular

Goodpasture’s syndrome: Anti-GBM Ab. Hemoptysis (2/2 to pulm hemorrhage). Attacks lungs & kidneys

Vasculitis: characterized by lack of immune deposits. +/- Anti-neutrophilic cytoplasmic antibodies (ANCA),
Vasculitis of small renal vessels (no room for microtubules, being attacked) thus RBC CASTS.

Alport’s syndrome aka hereditary nephritis: X-linked. Defect in collagen IV synthesis → splitting of the GBM
(fraying). Sx: hearing loss & eye changes. Progressive!
PRIMARY
Tx: Largely supportive, glucocorticoids, immunosuppressive, tx underlying disorder, refer

Minimal change disease: MC in children, associated with NSAID allergic rxn, lymphomas, leukemias, Sx: HTN,
edema, Tx: corticosteroids, may add cytotoxic agent [cyclophosamide, chlorambucil] Dx: electron microscop:
loss/fusion/diffuse effacement of the FOOT processes.

Membranous nephropathy: MC cause in nondiabetic adults. Thickening of GBM over time. Primary = idopathic.
Secondary = associated w/ Hep B antigenemia, autoimmune diseases, thyroiditis, malignancies & drugs (NSAIDs,
gold, penicillamine & captopril).

Focal segmental glomerulosclerosis: (FSGS): Sclerosis (fibrosis) w/in glomerulus. Idiopathic, HTN (esp in AA),
SLE, IgA nephropathy, vasculitis, HIV, IV heroin, interferon, pamidronate (dec osteoporosis => dec in Ca++). May
respond to steroids.

Membranoproliferative glomerulonephritis: (MPGN): least common, idiopathic or secondary to hepatitis C, Type I

- low C3 protein, Type II - dense deposit disease C3 is decreased, Sx: usually mixed nephritic-nephrotic picture

CYSTIC KIDNEY DISEASE

Renal Cysts: Can be genetic or non-genetic, affects children and adults, classified as simple or complex
Risk of malignancy increases with complex cysts

Bosniak Classification
Category I Benign simple cyst(s), thin wall, no septa, calcifications, or solid components, does non enhance
Management: no further workup required, poss repeat US at 6 to 12 months to confirm stability
Category II Well marginated, possibly some thin septa, possibly fine calcifications, uniformly
high-attenuation lesions that are less than 3cm in diameter, non-enhancing
Management: no further workup required, poss repeat US at 6 to 12 months to confirm stability
Category III Thickened, indeterminate masses, irregular or smooth septa, enhances, 40-60% are malignant (RCC)
Management: continued surveillance, Bx, Surg. Surgery preferred if good candidate, if not =
CT/MRI @ 6 mo w/ repeat yrly (CT or US)
Category IV Similar to Category III but also contain enhancing soft tissue components independent of the septa,
85-100% are malignant
Management: Surgery
Non-enhance: not vascularized, enhance: vascularized

Simple Renal Cysts: MC renal mass, common in normal kidneys, MC men + 50 yo, may be solitary / multiple,
unilateral / bilateral,

Sx: usually asymptomatic unless +5mm (hyperalbuminurea, HTN, hyper-filtration), it becomes infected or ruptures
(hematuria or flank pain).

Dx: incidental finding on US. Need 3 US criteria for benign cyst to be met, if not then CT scan. US Criteria: 1) Mass
is round & sharply demarcated w/ smooth walls 2) No echoes w/in mass aka clear fluid 3) Strong posterior wall echo,
indicating good transmission through the cyst. If not met...CT Criteria: Sharply demarcated, smooth thin wall, fluid
filled cyst is homogenous w/ density like water & no enhancing w/ contrast.

DDx: PKD (AD/AR), localized cystic disease (benign, unilateral & asx), malignancy (irregular septa, enhancement,
multilocular mass)

Tx: Majority don’t require tx, pain control with acetaminophen/NSAIDs, abx tx for infxn [fluoroquiniolones, Bactrim]
Acquired CKD: associated w/ CRI (peeps on dialysis), multiple bilateral renal cysts, usually < 0.5 cm but can be 2-3
cm. Dx: 4+ bilateral cysts present. Differentiated from inhered by having normal sized kidneys (vs large kidneys in
ADPKD)

Inherited cystic kidney disease: ADPKD, ARPKD, MSK

Differentiated from acquired cystic kidney disease by presence of LARGE kidneys

Autosomal dominant PKD: MC lift-threatening monogenic disease, affects all yall ethnic groups,

Etiology: complete penetrance. PKD1 = Most prevalent & worse prognosis. PKD2: Less prevalent & mild prognosis.

Sx: Asx till 50 yo. Bilateral renal cyst = huge kidneys (x4 in size, x20 in wt). 60% = flank & back pain & HTN. 40% =
renal cyst infection, gross hematuria, nephrolithiasis. (cyst infection=2nd MC cause of death). Uric acid stones.
Common to develop ERSD in late age. May have pancreatic or liver cysts (liver MC). Subarachnoid hemorrhage = 4-
5x more common w/ ADPKD pts. MVP. affects the nephrons (vs renal collecting ducts in ARPKD)

Dx: FHx, Renal US = multiple renal cysts bilaterally & for asx pts at risk. CT, MRI.

At risk pts: 2 cysts uni/bilaterally at 15-29 yo, 2 cysts bilaterally at 30-59 yo, 4 renal cysts bilaterally at 60+ yo

Tx: No tx, just can slow progression via inhibition of renin-angio system. BP control (X sodium, +statins), Sx control
(pain=NSAIDS & flow=flomax). 50% of pts will need dialysis/renal transplant. Decompressive surg for severe pain.

Px: most DIE from cardiac causes. Do you remember PKD1 gene pts have faster decline in renal function & poor
prognosis. (Other risk factors that play a role in renal function decline rate = HTN, early sx onset, male, large kidney
size, proteinuria, dec BF)

Autosomal Recessive PKD: worse form of PKD, significant in babies, PKHD1 gene mutation, cysts usually involve
collecting ducts

Sx: respiratory insufficiency, renal insufficiency/ESRD, HTN, hepatobiliary involvement

Dx: usually diagnosed in utero or during neonatal period d/t large echogenic kidneys, abdominal US findings [bilat
echogenic kidneys with poor corticomedullary differentiation, enlarged kidneys, hepatomegaly, hepatic cysts/dilation
of ducts], MRI/CT if US not definitive

Tx: supportive, perinatal/neonatal care, BP control, dialysis, transplant, possible liver transplant, genetic counseling to
parents

Px: dependent on renal/hepatic impairment, respiratory insufficiency - 30% will die shortly after birth, 60% will die
within 1 month, those who survive 1st month have chance to live to 15yoa

Medullary Sponge Kidney: not inherited, cystic dilation of collecting ducts, cysts vary in size, benign, Dx: incidental,
Complications: kidney stones [calcium phosphate and calcium oxalate], UTIs, reduced concentrating ability, nidus
formation [place where stones may continue to form]

RENAL CELL CARCINOMA

Renal Tumors: Benign = Oncocytoma & Renal Cell Adenoma. Malignant = RCC & Wilms Tumor

Wilms Tumor: MC kidney cancer in children, malignant, will get much larger than the kidney by the time it’s found,
unilateral, rarely metastasize, Sx: constipation, abd pain, nausea/vomiting, weakness/fatigue, loss of appetite, fever,
hematuria/discolored urine, HTN

RCC:MC renal malignant tumor. 2x more common in males @ 50-70 yo, usually over 40yoa,
Risk factors: cigs double the risk, dialysis, obese women, genetic factors, HTN, kidney transplant, occupation, cystic
kidney disease, chronic NSAIDs

Sx: hematuria, flank abd pain, palpable mass, many are asx until advanced disease, mainly localized tumor, if it
metastasizes, it’s to the lungs, scrotal varicosities (gonadal vein involvement), IVC involvement, paraneoplastic
syndromes (anemia), hypercalcemia (lytic bone metastasis++PTHRP), prostaglandin production, hepatic dysfunction,
cachexia, thrombocytosis, polymyalgia rheumatica

Dx: renal US to distinguish between complex cyst and tumor, if doesn’t meet benign criteria → gold standard: CT scan
with contrast (poorly demarcated walls, echos within cyst, poor posterior wall echo)
Patho: clear cell is MC, collecting duct most rare

Tx: based on staging, surgery is mainstay, localized: surgery, advanced: first line therapy (immunotherapy of IL2 and
interferon alpha), second line therapy (anti angiogenic VEGF pathway, mTOR inhibitors)

Classification: Stage I and II - localized, Stage III - regional,

Stage IV – metastatic

Summary: 1st s/sx = hematuria, CT gold standard, Surgery is

mainstay of Tx.

HYDRONEPHROSIS
Swelling of the kidneys, urine cannot drain

Epidemiology: common, all ages, in children it’s d/t congenital urinary tract defects, young adults d/t stones, old d/t
BPH

Etiology: MC urinary tract obstruction (stone, tumor, congenital defect, BPH) pregnancy or postpartum, excessive
diuresis, infxn, vesicoureteral reflux

Sx: low back/flank pain, changes in urine output, nausea/vomiting, fever, HTN, hematuria, increased serum creatinine
(if blockage is in BOTH kidneys), failure to thrive, asx in chronic condition, pain d/t stone, bladder distention or infxn,
NO pain in external compression of ureter

Dx: UA (infxn, hematuria), BMP (kidney function), chronic obstruction → hypercalcemia, KUB X-ray, renal US, CT
without contrast, cystourethrogram

Tx: symptomatic, treat underlying cause, UTI = stent, surgery w lithotripsy, infxn = Bactrim or ciprofloxacin,
nephrogenic DI = HCTZ, mild to moderate cases = observe, prophylactic abx

Px: depends on cause, severity, most functional recovery takes place in first 7-10 days if d/t urinary tract obstruction
RENAL VASCULAR DISEASE

RVD: Progressive condition that causes narrowing/blockage of the renal arteries or veins

Renal artery stenosis (RAS): Narrowing of one or more arteries that carry blood to the kidney

Fibromuscular dysplasia (FMD): Non-inflammatory, non-atherosclerotic disorder that leads to arterial stenosis,
aneurysm & dissection
Ischemic nephropathy: diminished renal blood flow → CKD

Pathophysiology: reduced perfusion pressure to kidneys activates RAAS, reduced sodium excretion, and activates
sympathetic adrenergic pathways → HTN → end organ damage/decreased renal function, RAS = d/t atherosclerosis,
narrowing of artery decreases BF to kidneys, FMD = genetic

Epidemiology: RAS: common over 65yoa, unilateral, FMD: incidental finding in kidney donors, women < 50yoa

Etiology: atherosclerosis (aka RAS), FMD, Risk factors: same as atherosclerosis & HTN

Sx: related to decreased kidney function with lack of secondary cause, severe HTN resistant to tx, acute elevation of
serum creatinine following ACEi/ARB, recurrent acute pulmonary edema/CHF, decreased renal function following
stenting of aorta, RAS: sx consistent with heart disease of PVD, FMD: stroke, MI d/t risk of dissection or ruptures,
severe/persistent HA, onset HTN before 35yoa, epigastric/abd/carotid bruit and pulsatile tinitis

Dx: renal arteriography, but don’t use in presence of renal failure, only do testing if there is high likelihood of
benefitting, FMD = digital subtraction angiography, Testing Criteria: secondary HTN, no primary kidney disease, no
pheochromocytoma, or no primary aldosteronism, Less invasive testing: duplex doppler US, CTA or MRA

Tx: 1) surgery revascularization w stent or bypass (beneficial in acute & rapid loss of kidney function, FMD &
prevent CKD progression), 2) Medical Tx (ACE/ARB) should focus on blocking RAAS, HTN control, & dec risk
atherothrombotic disease, tx comorbidities

Px: depends on degree of damage and age of presentation

Factors Favoring Medical Therapy and Revascularization for Renal Artery Stenosis
 Progressive decline in GFR during treatment of systemic hypertension
 Failure to achieve adequate blood pressure control with optimal medical therapy (medical failure)
 Rapid or recurrent decline in the GFR in association with a reduction in systemic pressure
 Decline in the GFR during therapy with ACE inhibitors or ARBs
 Recurrent congestive heart failure in a patient in whom the adequacy of left ventricular function does not explain a cause
Factors Favoring Medical Therapy and Surveillance of Renal Artery Disease
 Controlled blood pressure with stable renal function (e.g., stable renal insufficiency)
 Stable renal artery stenosis without progression on surveillance studies (e.g., serial duplex ultrasound)
 Very advanced age and/or limited life expectancy
 Extensive comorbidity that make revascularization too risky
 High risk for or previous experience with atheroembolic disease
 Other concomitant renal parenchymal diseases that cause progressive renal dysfunction (e.g., interstitial nephritis,
diabetic nephropathy)

ACUTE KIDNEY INJURY (AKI) / FAILURE

Creatinine:  GFR 50% =  in Cr from 1  2. Monitors kidney function & used to estimate GFR.
Factors affecting Cr = 1) Muscle mass, 2) creatine intake & 3) drugs like ACEi/ARBs (dilate EA & GFR), NSAIDs
(constrict & GFR), diuretics (plasma vol & GFR). *any  greater than 1-1.5mg/day = suspicious for Cr
production, ie rhabdomylolysis

Bun: bun = GFR, protein intake or GI bleed. Relates metabolic function of liver & excretory function of kidney.

When BUN is elevated, pts have azotemia. When thy are symptomatic, they have uremia.
Sx at toxic urea levels include: Anorexia, anemia, weight loss, N/V/D, dyspnea, taste disturbance,
Fractional excretion of Sodium (FENa): used to compare the amt of Na in urine vs amount of
Na in serum
FENA in ATN (intrinsic AKI):  tubular reabsorption of Na+ thus  Na in urine
FENA in Pre-renal AKI: Na reabsrp in proximal tubule

Acute Kidney Injury = asx, abrupt  in kidney function that results in retention of urea & other nitrogenous waste
products & in dysregulation of extracellular volume & electrolytes. All function can b repaired.
*BUN:Cr ratio used to assess cause of AKI.
 Renal perfusion  Na reabsorption to maintain BV   BUN THUS  BUN:Cr.

PRERENAL: MC type of AKI!! d/t mild-mod renal hypoperfusion (hypovolemia). Rapidly reversible with volume
repletion of BF but will lead to intrinsic AKI (ischemic injury) if not corrected. Prerenal AKI induces hypovolemia,
CO, systemic vasodilation.
Etiology: Intravascular vol depletion (hemorrhage, GI loss=V/D, diuretics, burns) Meds (ACEi, ARBs, NSAIDs)
 CO (cardiogenic shock, CHF, PE) Sequestration in 3rd spaces (Ascites, nephrotic synd, intestine obstruction)
Inadequate fluid replacement Systemic vasodilation (anaphylaxis, antihypertensive drugs, sepsis)
Systemic/renal vasoconstriction (anesthesia, surg,  [dopamine])

Patho: Hypoperfusion induces comp mech (autoregulation try to maintain GFR & BF by AA dilation & EA constriction)
Failure to dx early  renal parenchymal ischemia w/ tubular injury & GFR

Sx: urine output, labs: BUN:Cr, FeNa. PE = evidence of dehydration, shock vs overload.

Dx: Hx = V/D, CHF, poor oral intake, aggressive diuretics, NSAIDs PE = Tachycardia, orthostatic & systemic hypotension,
dry mucous membrane, thirst,  jugular vein pressure,  skin turogor, urine output. Labs =  BUN/Cr > 20:1 & FeNa<1%

Tx: aggressive normalization of arterial volume  IV (be careful w/CHF & elderly pts), correct underlying cause

INTRINSIC: d/t anything involving portion of nephron/interstitium.

Classified by primary histologic site of injury (1) tubules=ATN, 2) interstitium=AIN, 3) glomerulus 4) vasculature)

1) ATN: Acute Tubular Necrosis = MC intrarenal disease, damage to renal tubules, 50% = occurs MC secondary to
ischemia [prolonged hypovolemia / progression from prerenal) 25% = renal toxins. Dx: MUDDY brown casts in UA w/
microscopy are pathognomonic for ATN.
Renal toxins: direct damage (aminoglycoside abx, IV radiocontrast, rhabdomyolysis) Indirect damage
(vasoconstriction = radiocontrast, NSAIDs), precipitation of drugs that cause intratubular obstruction (sulfas,
acyclovir & MM light chains).
Tx: conservative management, avoid further insults, correct fluid probs.
2) AIN: Acute Interstitual Nephritis = 2/2 to damage to renal interstitium.
Etiology: penicillins, cephalosporins, sulfas, NSAIDs. Bacterial, viral infections, AI ( SLE, Sjogrens, cryoglobulinemia)
Acute: inflammatory lesions (diffuse/patchy) by T lymph, monocytes, macrophages & granulomas (hypersensitive rxn)
Chronic: interstitual fibrosis, tubular atrophy, foci of inflammatory cells. Triad = fever, rash, eosinophilia. WBC casts,
WBC casts. Tx: withdraw offending haters, some prednisone on the side for a short while could help.

3) Glomerulonephritis: LC cause. Direct inflammatory glomerular injury (from SLE, wegner’s granulomatosis,
goodpasture’s syndrome, HUS) Dx: RBC casts or gross proteinuria. Need Renal Bx (nephritic syndrome)

POSTRENAL: obstruction of collecting system (luminal flow of glomerular filtrate), so distal to kidneys. Continued
filtration leads to intraluminal pressure upstream to site of obstruction…effentially unable to maintain GFR. Function
declines so renal BF & GFR if not relieved w/in 12-24hrs.  in BUN&Cr.

Eti: Obstruct urethral meatus & bladder neck OR bladder neck (BPH, prostatitis, prostate/cervical CA stone).
Bilateral ureteral obstruction (calculi, bladder/colon/pelvic CA, lymphomas). Unilateral obstruction (gots 1 kidney).
Neurogenic bladder, anticholinergic drugs (Benadryl, Vesicare), intratubular crystals, will see in UA (uric acid, Ca++)

Dx: Hx of obstruction (see above eti + nocturia, freq, hesitancy). PE = suprapubic/flank pain. Do Renal US.
Labs = Oliguria<450mL/day & anuria<100ml/day. BUN & Cr ONLY. Bladder cath can be dx & tx.

Tx: BPH (bladder cath), Outlet obstruction from stones (ureteral stenting, precut nephrostomy tubes)

DIALYSIS: AEIOU = metabolic Acidosis, Electrolyte abn, Intoxicants, fluid Overload unresponsive to Tx, Uremia sx

CHRONIC KIDNEY DISEASE:

Refers to all problems that follow the progressive loss of kidney function

Two characteristics:
“Chronic” because loss of function is rarely repaired
Progressive and causes more damage even if insult is removed

MC caused by diabetes and HTN (70%), Epidem: elderly, African Americans, CV disease

Patho: HTN: increased pressure to afferent aa. and glomerulus causes sclerosis/damage, ACE/ARB tx prevents
hyperfiltration & damage by vasodilating efferent aa. and decreasing pressure on glomerulus, Albuminuria: toxic to
the kidney and causes cell damage, pts with higher albuminuria have most RAPID loss of function, ACE/ARB
decrease albuminuria and also protect glomerulus from HTN damage, lower albuminuria = slow the loss of function

Sx: NONSPECIFIC even late in the disease, MC discovered when pt is HTN with increased BUN/creatinine, many pts
report “exercise intolerance, fatigue, anorexia,” kidney stone, uremia, hyperkalemia, anemia (d/t decreased
erythropoietin production), osteoporosis

Dx:
Proteinuria is BEST indicator of disease progression
Progression of CKD based on urinary albumin level:
30-300 mg/day = microalbumin  consider adding or increasing ACE
300-1000 mg/day = overt nephropathy
UA, estimated GFR, BUN/creat
US to assess ureters/bladder/kidney size, amyloidosis, hemochromatosis (too much iron),
 Large kidneys  diabetes, HIV nephropathy (we know about this!), infiltrative disease
Small kidneys with loss of cortex  chronic glomerular disease, renal artery stenosis
Difference in size  renal artery stenosis, esp if HTN

Tx: Stage 1 and 2 – goal is PREVENT CV disease and further loss of function  reduce BP, control glucose in
diabetics, d/c smoking, monitor and lower albuminuria and loss of GFR [check annually in diabetic and HTN pts],
ACE/ARB, add statin based on CV risk,
Stage 3 and 4 – REFER, maintain renal blood flow  loop diuretics preferred at this point because thiazides are
ineffective when GFR < 25, control HTN, dietary sodium restriction 2 g/day to avoid fluid overload, protein restriction
to 0.8 g of protein/kg ideal body wt, be aware of medications that will cause complications [NSAIDs],
ESRD/Stage 5 – transplant is tx of choice, dialysis 3x wk, fluid overloaded pts  emergency dialysis may be
indicated, CV disease is MC cause of mortality in dialysis pts
Px: 1/3 pts with stage 4 CKD will progress to ESRD within 3 yrs

STAGES = risk of progression to ESRD/GERD rises when pt has

GFR below 60; normal GFR = 120-130

RISK FACTORS FOR PROGRESSION: HTN, albuminuria, nephrotoxic damage from high protein diets and meds,
smoking, obesity

RENAL FUNCTIONS DIALYSIS REPLACES: waste removal and fluid balance

COMPLICATIONS DURING DIALYSIS: hypotension, infxn, cramps, nausea/vomiting, HA, chest pain d/t less
blood perfusion in the heart, hyperkalemia  arrhythmias, back pain. Itching, fever/chills