World Veterinarian Prize Quiz - 2

Anatomy of Kidney

The two kidneys lie against the back abdominal wall, lateral to the spine, in the lumbar region.

Left kidney is located caudally and right kidney cranially to head.

Role of Kidney

Bone health

Blood pressure

Acid – base balance

Erythropoietin

Water regulator

Renal dysfunctions

Renal insufficiency: >70% loss of functional mass= Loss of concentrating ability leading to dilute urine.

Risk factor

Age:Highest risk factor at age of >8 years, sometimes 4-8 years and lowest risk factor at age of <4 year.

Gender: It is not specific but higher in female than male

Breed:  Labrador > German shepherd > Pomerian

Disease: Systemic Infectious disease

                Cardiovascular disorder and obstructive causes 

Food: High phosphorus and high protein rich diet and            

Managmental: Obesity, trauma and expose to toxin  

Etiological Agent

Infectious cause:

A.      Viral infection : it is not specific right now

B.      Bacterial infection : Leptospirosis , Pyelonephritis

C.      Haemoprotozoan infection : Borelliosis,

Systemic causes:

A.      Sepsis

B.      Urolithiasis

C.      Nephroliths

D.     Hyper calcemia

Drugs:

A.      Aminoglycosides

B.      NSAIDs

C.      ACE blockers

D.     Radiographic agent

Miscellaneous:

A.      Ischemia

B.      Shock

C.      Infraction

D.     Pancreatitis

Clinical Sign:

Persistent Vomiting.

Polyuria-polydipsia followed by oliguria.

Various degree of dehydration.

Anaemia

Lethargy, halitosis and paresis

Haemorrhages on buccual mucosa and melena

Oedema of hind limbs

Ascites

Diagnosis

1.       History and Clinical Signs

2.       Physical examination

3.       Urine analysis

4.       Haematology

5.       Serum Biochemistry

6.       Biomarkers

7.       Ultrasonography and Radiography

8.       Biopsy

Urine Analysis

Non-invasive method of assessing the function of kidney.

Fresh urine should be collected for analysis either through direct voiding (mid–stripe) or catheter.

Physical Examination of Urine

Parameters	Normal	Alterations
Color	Yellow due to Urochrom	Deep yellow–Dehydration Colorless –Diluted / Isothuria
Volume	20-25 ml/kgB.wt./day	Polyuria-Earlystage Oligouria-Later stage Anuria-End Stage
Specific Gravity	1.015-1.030	Increased -Early stage (1.050-1.076:5% dehydration) Decreasein -Later stage

Chemical Examination of Urine

Parameters	Normal	Alteration
pH	5.0 –7.5	•Decrease–Acidosis, Protein rich diet •Increase–UTI, diuretics, alkalosis
Glucose	Not present	>180mg/dL–Diabetes Mellitus
Blood	Not present	Haemoglobinuria(Haemolysis, Autoimmune reaction), Haematuria(Trauma)
Protein	Trace <50mg/dL	If higher (++) suggestive of •Renal damage, glomerulonephritis, cystitis and urethritis. •Non-renal causes: PLE, hemo and myoglobinuria, heavy exercise and diet

Hyaline casts -Mild stage of renal impairment.

Granular casts– it is the hallmark of acute kidney injury due to ischemia, protein induced nephropathy viz. haemoglobin and myoglobin, administration of nephron toxic drugs etc.

Epithelial cell casts -Acute nephritis and cystitis.

Fatty casts –Damage in renal tubules seen in DM.

Erythrocytic casts –Haemorrhage in the kidney /RT.

Leukocytic casts -Inflammation and Sepsis.

Haematology

Normocytic normochromic and regenerative anaemia is commonly observed in acute form while Non-regenerative anaemia is one of the common findings in dogs with chronic kidney dysfunctions.

PCV is usually increased.

Neutrophilia and leucocytosis suggest sepsis.

In renal disorders due to hemoprotozoan infections, thrombocytopenia is a common finding.

Serum Biochemistry

In General screening following tests are to be done for assessing degree of renal damage.

1.      Blood Urea Nitrogen / Urea

2.      Creatinine

3.      Sodium and Potassium

4.      Phosphorous and Calcium

5.      Total protein

Urea and BUN(Normal:10-30mg/dL):

Urea is end product from ammonia derived from protein catabolism within the liver and filtered at glomerulus.

Urea is about 2.14 times than BUN Thus, BUN 10mg/dL is equivalent to urea 21.4mg/dL.

It is an insensitive indicator of reduced GFR.

When GFR reduced by around 50% ,BUN gets elevated above the upper limit.

 

Creatinine (Normal:0.5-1.5mg/dL):

It is produced from dehydration of creatine and dephosphorylation of phosphocreatinein muscle.

It specific indicator of renal involvement but less reliable because its elevation seen when 75%loss of functional nephrons.

Creatinine has an exponential relationship with GFR.

Hence, normal creatinine values can camouflage the renal involvement in routine clinical practice.

Hyperphosphetemia

Whenever decrease the GFR rate and increase Phosphorus concentration in kidney so there is poor calcium absorption so there will be also decrease calcitrol and increase parathyroid hormone which lead demineralization of bone and increase the phosphorus in tissue.

Hypokalaemia 

The ability to maintain potassium extraction at near normal level in generally maintained by aldosterone secretion and distal flow rate

Common source of low aldosterone level are Diabetes mellitus, use of ACE inhibitors, NSAIDs or beta blockers

Hyperkalaemia is consistent finding in advanced stages of kidney disease.

Symmetric dimethylated arginine (SDMA)

It is a sensitive indicator of kidney function that detect as little as 25% loss of function

It is not influenced by muscle mass and an early indicator of progressive kidney function loss as well as concurrent disease that may have a secondary impact of kidney function

Biomarkers of kidney dysfunction

Urinary markers of glomerular dysfunction

Albumin microalbuminuria

C reactive protein acute phase proteins with and increased serum concentration in inflammatory disease

Due to its size 115 k Dalton CRP is not able to pass through the impact glomerular barrier the presence of CRP in urine is the result of glomerular dysfunction

Ultrasonography

Ultrasound is the ideal imaging test of evaluating Kidney Disease because it provides information about the position site safe internal architecture of Kidneys without harming the patient

Disease of kidney treatment by ultrasonography can be divided into

1.      Diffuse: nephritis ESKD

2.      Regional: hydronephrosis PN and nephroliths

3.      focal for multifocal like cyst or Polycystic in renal disease.

Measurement of renal size by

                                                              i.      Renal : centimetre 

                                                            ii.      Kidney and Aorta (K/Ao) = 5.5 to 9.1 centimetre

Radiography

It is useful to determine chronic kidney is function when mineralization from bone mineralization to other tissue developed.

 

Renal biopsy 

Renal biopsy is considered for patient with…

Persistent substantial proteinuria

Unresponsive to antiproteinuric therapy

Suspecting renal mass and CKD in young dogs

Glucose platelet buccal mucosal bleeding time and blood pressure should be with reference range

 

Acute kidney dysfunction (AKD)

The functional or structural abnormalities for markers of kidney damage including abnormalities and blood urine or tissue test for imaging study present for less than 3 months

 

AKI Grade	Serum Creatinine (mg/dl)		Clinical description
Grade 1	<1.6		Non azotemic AKI •Clinically oliguria/anuria, •Nausea/vomition •Elevation/ detection of biomarker
Grade 2	1.7-2.5		Mild AKI •Increase in S.Creatinine≥ 0.3 mg/dl within 48 h and VR: < 1ml/kg/h over 6 h
Grade 3	2.6-5.0		Moderate to Severe AKI •Severities of clinical signs due
Grade 4		5.1-10.0

 

 

Chronic kidney dysfunction

Structural and functional impairment of one or both Kidneys that has been present for more than approximately 3 month

Security is considered as disease of an older animals although it covers at all ages

Stage	Blood Creatinine (mg/dl )	Serum SDMA (μg/dl)	Comments
1	1.5	14-18	Protinuria, Structural and function changes
2	1.4 –2.8	18 -35	Mild systemic signs
3	2.9 –5.0	36 -54	Moderate systemic sign
4	>5.0	>54	Marked systemic and Uremic sign

Differentiating points of AKI to CKI

PARAMETERS	ACUTE	CHRONIC
Clinical signs	Anorexia, lethargy and voimition	Azotaemia more severe than clinical signs
Water Intake/ Urine ,Body Cond.	Reduced, Good	PU/PD, weight loss
Kidney size/ shape	Normal/large with Pain	Small and irregular architecture and no pain
Haematology	Non anaemic, PCV increased	Non-regenerativeanemia
K   P	Normal to high   High	Mild hyperkalemia   High
Urine SG	Pre Renal: > 1.030 Renal : 1.008 -< 1.030	1.008 -1.015

 

Principle of treatment

NEPHRONS

N management of Nutrition

E balance electrolytes

P regulate blood pressure and proteinuria phosphorus

H management of hydration

R management of retention of substance

O other renal insult avoid

N management of neuroendocrine function

S serial monitoring of patient

Management of dehydration

Degree of Dehydration (%)	Eye ball position	Skin tenting (sec.)	HCT (%)	Mucous Membrane of eye	Capillary Refill Time (Sec)
Normal	Normal	<1	40	Moist	< 2
1-5	Normal	1-4	40-45	Moist	2
6-8	Slightly sunken	5-10	50	Tacky	2-3
9-10	Gap between eyeball and surrounding tissue	11-15	55	Tacky to dry	4
11-12	Large gap and very sunken	16-45	60	Dry	>4

 

Place IV catheter and urinary catheter

Fluid replace = percentage of dehydration × body weight in kg within 24 hours

5% dehydration on always present when kidney insult is established so it is replaced it within 2 to 4 hours

Maintenance fluid is to be given at 44 to 66 ml/kg/day

Choice of fluid will be RL solution, if not hyperkalemia. Otherwise 0.9 percentage sodium chloride

Give 10 ml/kg IV crystalloid, if no output of urine go for diuresis

Management of Oliguria or Anuria

When fluid therapy initiated urinary flow should be rapidly increased to >2 ml/kg body/hour

Oliguria:  <0.5 to 1 ml/kg/hour in spite of fluid therapy

Furosemide: Loop diuretic and first choice

It will increase urinary flow without increasing GFR

It has been renal vasodilatory effect

It inhibit Na, Cl  and K pump in luminal cell of loop of henle

Dose: 2 ml/kg intravenously urine output is 30 to 60 min. If escalate dose at 4-6 ml/kg body weight after 1 hour

CRI : 0.66 mg/kg/hr has been effective in dog

20% mannitol osmotic diuresis second choice

It helps in extracellular volume expansion and inhibit renal sodium absorption by acting as an antagonist

Increase renal blood flow GFR scavenging free radicals and solute excretion

Dose 0.5 to 1 gram/kg body weight within 20 min. Urine flow increase within our and repeat every 6 hours

CRI: 1 ml/kg/min intravenously

Avoid using oliguric patient with volume overloaded or 20% dextrose 22-66 ml/kg/day (2-10 ml/min)

Balance of electrolyte

Metabolic acidosis is commonly occur in acute kidney and chronic kidney infection

Alkalizing therapy should not be recommended unless blood pH is less than 7.2 or serum bicarbonate level is less than 40 mEq/litre after correcting fluid deficit

Give 1/4 to 1/2 dose directly by slow IV and remaining in IV fluid over for 4 - 6 hour

Hyperkalemia

Renal excretion in the major mechanism of removal of K from body

It is life threatening not control

Insulin 0.5 unit/kg body weight IV followed by dextrose 2 gram (40ml 5D)/unit of insulin. Or 10% calcium gloconate at 0.5-1 ml/kg Slow IV will restore cardiac abnormality within a minute

Management of neuroendocrine function

Renal secondary hyperthyroidism occur commonly with CKD because of phosphorus retention and decrease calcitriol

Calcitriol stimulant gastrointestinal absorption of calcium and phosphorus inhibit parathyroid hormone production

Calcitriol 2 - 3 ml/kg/ day  oral after dissolution of hypercalcemia and hyperphosphatemia

Hypoproliferative anaemia Hallmark of kidney dysfunction

It has been shown that patient with chronic kidney disease have increased survival If the haematocrit it is about 35%.

Human Recombinant erythropoietin can be given at off 100 IU/kg body weight SC trice in week

Darbepoetin, long acting erythropoietin also be used at 1mcg/kg body weight SC once in a week

Blood pressure

Risk assessment	Systolic BP (mmHg)	DiastolicBP (mmHg)	Breed specific
Minimal risk Normotension(N)	<150	< 95	<10mmHg
Low risk Borderline hypertension (BP)	150-159	95-99	10-20mmHg
Moderate risk Hypertension (H)	160-179	100–199	20-40mmHg
High risk Severe Hypertension( SH)	>180	>120	>40mmHg
Risk not determined		No Blood Pressure not measured

 

Drugs for Gastro-intestinopathy

For the control of Vomition:

1.      Odansetron: 0.5 mg/kg b.wt. IV at every 6 hrs.

2.      Metaclopromide: 0.2 mg/kg b.wt.IVat every 8 hrs.

3.      Maropitant: 1mg/kg b.wt. SC SID < 5 days.

For the control of Gastric Ulcer:

1.      Ome/ Penta-prazole(PPI) : 1mg/kg b.wt. IV/PO SID.

2.      Sucralfate: 0.5 –1gm/kg b.wt. POTID

 Nutritional management

Protein restriction: BUN>80mg/dl, high P & Creatinine 2.5mg/dl.

Renal diet is required generally with CKD stage II–IV where proteinuria is an evident.

Diet should have sufficient calories (70kcal/kg/day) to stop protein catabolism.

No sodium restriction required.

Supplementation of Omega-3PUFAs (notO-6) have shown reno-protective anti-inflammatory properties.

Commercial available renal wet diet is preferable.

 

Renal Replacement Therapy(RRT)

Indications:

·         When dog failed to respond medical management.

·         Severe hyperkalamia(>8 mEq/L), hyperphosphetemia(>10 mg/dL).

·         Persistent uraemia signs.

·         Patient with AKD has more appropriate than CKD.

RRT can only extend longevity for few months and provides wellbeing of kidney patients at high cost.

Peritoneal dialysis: removes uremic toxins by diffusion from the peritoneal membrane.

Extracorporeal Renal Replacement Therapy(ERRT) removes uremic toxins by diffusion and/ conventions from blood; can be performed by Intermittent Haemodialysis(IHD) and Continuous Renal Replacement Therapy(CRRT) units.

Prognosis of kidney dysfunction

Despite all the advances, about 60% of dogs with this disease either die or are humanely euthanized because of failure to respond to supportive care.

For dogs with severe ARF treated with haemodialysis survival was nearly 80% for dogs with infectious causes, 40% for dogs with non-infectious and non-toxic etiologies.

Decreased urine production and hyperkalaemia are poor prognostic factors in dog kidney dysfunction.

Mean survival time for CKD patients is 226 days based of IRIS stages.

 

 

References:  (IRIS, 2019)

Special thanks to Dr.Sudhir A. Maheta , assistant professor, Department of veterinary medicine, NAU, Gujarat.